Mast cells have been most widely studied in the context of allergic disease, but they have been clearly shown to have a crucial role in host defence in vivo against several bacterial and parasitic infections.
Mast cells are found in large numbers at sites that are exposed to the external environment, such as the skin, airways and intestine, and are frequently located close to blood vessels and nerves. Residing in this location allows mast cells to have a sentinel role in early host defence.
Mast cells produce three main classes of mediator — pre-formed granule-associated mediators, lipid-derived mediators, and a wide variety of cytokines and chemokines — which allow mast cells to initiate and modify physiological responses and immune function.
Mast cells can selectively produce different classes of mediator and alternative profiles of cytokines and chemokines in response to specific pathogens and their products, thereby allowing the selective activation and recruitment of specific cell types, such as neutrophils, eosinophils, dendritic cells and T cells.
Mast cells express a wide range of direct and indirect receptors, which provide a mechanism for selective responses to pathogens. These include Toll-like receptors, Fc receptors and complement receptors.
Mast cells have an important role in initiating the recruitment of effector cells that are appropriate for fighting infection with different types of pathogen. This occurs through the selective production of mediators that can activate endothelial cells, increase vascular permeability and provide chemotactic signals to other immune-effector cells.
In addition to well-documented effects on innate immune function, mast-cell activity can also influence the acquired immune response, particularly through 'activation' of lymph nodes and interactions with dendritic cells.
The ability of mast cells to respond to pathogens, although important to host survival in some situations, might also have detrimental effects. Mast-cell responses to pathogens could contribute to the pathology of allergic disease and to other chronic inflammatory conditions.
Mast cells have mainly been studied in the setting of allergic disease, but the importance of mast cells for host defence against several pathogens has now been well established. The location of mast cells, which are found closely associated with blood vessels, allows them to have a crucial sentinel role in host defence. The mast cell has a unique 'armamentarium' of receptor systems and mediators for responding to pathogen-associated signals. Studies of this intriguing immune-effector cell provide important insights into the complex mechanisms by which appropriate innate and acquired immune responses are initiated.
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Echtenacher, B., Mannel, D. N. & Hultner, L. Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381, 75–77 (1996).
Malaviya, R., Ikeda, T., Ross, E. & Abraham, S. N. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α. Nature 381, 77–80 (1996). References 1 and 2 were the first to show a crucial role for mast cells in host defence against bacterial infection in vivo . They also indicated that TNF is an important mediator of this response.
Galli, S. J., Maurer, M. & Lantz, C. S. Mast cells as sentinels of innate immunity. Curr. Opin. Immunol. 11, 53–59 (1999).
Tertian, G., Yung, Y. P., Guy-Grand, D. & Moore, M. A. Long-term in vitro culture of murine mast cells. I. Description of a growth factor-dependent culture technique. J. Immunol. 127, 788–794 (1981).
Nakano, T. et al. Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J. Exp. Med. 162, 1025–1043 (1985).
Tsai, M. et al. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. Proc. Natl Acad. Sci. USA 88, 6382–6386 (1991).
Tsai, M. et al. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J. Exp. Med. 174, 125–131 (1991).
Schrader, J. W., Lewis, S. J., Clark-Lewis, I. & Culvenor, J. G. The persisting (P) cell: histamine content, regulation by a T cell-derived factor, origin from a bone marrow precursor, and relationship to mast cells. Proc. Natl Acad. Sci. USA 78, 323–327 (1981).
Ihle, J. N. et al. Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, P cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J. Immunol. 131, 282–287 (1983).
Kitamura, Y. & Go, S. Decreased production of mast cells in S1/S1d anemic mice. Blood 53, 492–497 (1979).
Kitamura, Y., Go, S. & Hatanaka, K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52, 447–452 (1978).
Madden, K. B. et al. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J. Immunol. 147, 1387–1391 (1991).
Saito, H. et al. Selective growth of human mast cells induced by Steel factor, IL-6, and prostaglandin E2 from cord blood mononuclear cells. J. Immunol. 157, 343–350 (1996).
Costa, J. J. et al. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J. Exp. Med. 183, 2681–2686 (1996).
Enerback, L. & Lowhagen, G. B. Long term increase of mucosal mast cells in the rat induced by administration of compound 48/80. Cell Tissue Res. 198, 209–215 (1979).
Befus, A. D., Pearce, F. L., Goodacre, R. & Bienenstock, J. Unique functional characteristics of mucosal mast cells. Adv. Exp. Med. Biol. 149, 521–527 (1982).
Bienenstock, J. et al. Comparative aspects of mast cell heterogeneity in different species and sites. Int. Arch. Allergy Appl. Immunol. 77, 126–129 (1985).
Selye, H. Mast cells and necrosis. Science 152, 1371–1372 (1966).
Heavey, D. J. et al. Generation of leukotriene C4, leukotriene B4, and prostaglandin D2 by immunologically activated rat intestinal mucosa mast cells. J. Immunol. 140, 1953–1957 (1988).
Pearce, F. L., Befus, A. D., Gauldie, J. & Bienenstock, J. Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells. J. Immunol. 128, 2481–2486 (1982).
Irani, A. A., Schechter, N. M., Craig, S. S., DeBlois, G. & Schwartz, L. B. Two types of human mast cells that have distinct neutral protease compositions. Proc. Natl Acad. Sci. USA. 83, 4464–4468 (1986).
Irani, A. M. et al. Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. J. Immunol. 138, 4381–4386 (1987).
Mayrhofer, G. & Bazin, H. Nature of the thymus dependency of mucosal mast cells. III. Mucosal mast cells in nude mice and nude rats, in B rats and in a child with the Di George syndrome. Int. Arch. Allergy Appl. Immunol. 64, 320–331 (1981).
Irani, A. M., Butrus, S. I., Tabbara, K. F. & Schwartz, L. B. Human conjunctival mast cells: distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis. J. Allergy Clin. Immunol. 86, 34–40 (1990).
Gotis-Graham, I. & McNeil, H. P. Mast cell responses in rheumatoid synovium. Association of the MCTC subset with matrix turnover and clinical progression. Arthritis Rheum. 40, 479–489 (1997).
Bienenstock, J. et al. The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions. Int. Arch. Allergy Appl. Immunol. 82, 238–243 (1987).
Stead, R. H. et al. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Proc. Natl Acad. Sci. USA 84, 2975–2979 (1987).
Starkey, J. R., Crowle, P. K. & Taubenberger, S. Mast-cell-deficient W/Wv mice exhibit a decreased rate of tumor angiogenesis. Int. J. Cancer 42, 48–52 (1988).
Coussens, L. M. et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 13, 1382–1397 (1999).
Compton, S. J., Cairns, J. A., Holgate, S. T. & Walls, A. F. The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: tryptase induces expression of mRNA for IL-1β and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. J. Immunol. 161, 1939–1946 (1998). This report showed that tryptase secreted by human mast cells can activate endothelial cells and initiate the production of CXCL8.
Huang, C. et al. Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6. J. Immunol. 160, 1910–1919 (1998). This paper established that a specific protease secreted by mouse mast cells can selectively induce neutrophil recruitment in vivo.
Algermissen, B., Hermes, B., Feldmann-Boeddeker, I., Bauer, F. & Henz, B. M. Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars. Exp. Dermatol. 8, 193–198 (1999).
Muramatsu, M., Katada, J., Hayashi, I. & Majima, M. Chymase as a proangiogenic factor. A possible involvement of chymase–angiotensin-dependent pathway in the hamster sponge angiogenesis model. J. Biol. Chem. 275, 5545–5552 (2000).
Compton, S. J., Cairns, J. A., Holgate, S. T. & Walls, A. F. Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC). Clin. Exp. Immunol. 121, 31–36 (2000).
Davidson, S., Gilead, L., Amira, M., Ginsburg, H. & Razin, E. Synthesis of chondroitin sulfate D and heparin proteoglycans in murine lymph node-derived mast cells. The dependence on fibroblasts. J. Biol. Chem. 265, 12324–12330 (1990).
Gilead, L. et al. Human gastric mucosal mast cells are chondroitin sulphate E-containing mast cells. Immunology 62, 23–28 (1987).
Di Nardo A., Vitiello, A. & Gallo, R. L. Mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J. Immunol. 170, 2274–2278 (2003).
Leal-Berumen, I., Conlon, P. & Marshall, J. S. IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. J. Immunol. 152, 5468–5476 (1994). This paper showed that mast cells can respond to LPS and produce cytokines independently of degranulation.
Gupta, A. A., Leal-Berumen, I., Croitoru, K. & Marshall, J. S. Rat peritoneal mast cells produce IFN-γ following IL-12 treatment but not in response to IgE-mediated activation. J. Immunol. 157, 2123–2128 (1996).
Supajatura, V. et al. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J. Clin. Invest. 109, 1351–1359 (2002). This report contrasted the important roles of TLR2 and TLR4 expressed by mast cells for stimulating the production of mediators and for responding to local inflammation in vivo.
Supajatura, V. et al. Protective roles of mast cells against enterobacterial infection are mediated by Toll-like receptor 4. J. Immunol. 167, 2250–2256 (2001).
McCurdy, J. D., Olynych, T. J., Maher, L. H. & Marshall, J. S. Distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells. J. Immunol. 170, 1625–1629 (2003).
Varadaradjalou, S. et al. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. Eur. J. Immunol. 33, 899–906 (2003).
Marshall, J. S., Leal-Berumen, I., Nielsen, L., Glibetic, M. & Jordana, M. Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. J. Clin. Invest. 97, 1122–1128 (1996).
McCurdy, J. D., Lin, T. J. & Marshall, J. S. Toll-like receptor 4-mediated activation of murine mast cells. J. Leukoc. Biol. 70, 977–984 (2001).
Zhu, F. G. & Marshall, J. S. CpG-containing oligodeoxynucleotides induce TNF-α and IL-6 production but not degranulation from murine bone marrow-derived mast cells. J. Leukoc. Biol. 69, 253–262 (2001).
Matsushima, H., Yamada, N., Matsue, H. & Shimada, S. TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J. Immunol. 173, 531–541 (2004).
Kulka, M., Alexopoulou, L., Flavell, R. A. & Metcalfe, D. D. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J. Allergy Clin. Immunol. 114, 174–182 (2004). References 47 and 48 established that TLR3- and TLR7-mediated activation can induce selective secretion of mediators by subsets of mast cells in rodents and humans.
Heil, F. et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303, 1526–1529 (2004).
Okumura, S. et al. Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcεRI. Blood 102, 2547–2554 (2003).
Malaviya, R., Gao, Z., Thankavel, K., van der Merwe, P. A. & Abraham, S. N. The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. Proc. Natl Acad. Sci. USA 96, 8110–8115 (1999).
Woolhiser, M. R., Okayama, Y., Gilfillan, A. M. & Metcalfe, D. D. IgG-dependent activation of human mast cells following up-regulation of FcγRI by IFN-γ. Eur. J. Immunol. 31, 3298–3307 (2001). This paper showed that the expression of FcγRs is upregulated by human mast cells following treatment with IFN-γ and that these cells are activated following recognition of IgG-containing immune complexes.
Genovese, A. et al. Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E. Infect. Immun. 68, 5517–5524 (2000).
Patella, V., Florio, G., Petraroli, A. & Marone, G. HIV-1 gp120 induces IL-4 and IL-13 release from human FcεRI+ cells through interaction with the VH3 region of IgE. J. Immunol. 164, 589–595 (2000).
Genovese, A. et al. Protein Fv produced during viral hepatitis is an endogenous immunoglobulin superantigen activating human heart mast cells. Int. Arch. Allergy Immunol. 132, 336–345 (2003).
Jarrett, E. E. & Miller, H. R. Production and activities of IgE in helminth infection. Prog. Allergy 31, 178–233 (1982).
Verwaerde, C. et al. Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni. J. Immunol. 138, 4441–4446 (1987).
Gurish, M. F. et al. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J. Immunol. 172, 1139–1145 (2004).
Nilsson, G. et al. C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway. J. Immunol. 157, 1693–1698 (1996).
Fureder, W. et al. Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J. Immunol. 155, 3152–3160 (1995).
Weber, S., Babina, M., Feller, G. & Henz, B. M. Human leukaemic (HMC-1) and normal skin mast cells express β2-integrins: characterization of β2-integrins and ICAM-1 on HMC-1 cells. Scand. J. Immunol. 45, 471–481 (1997).
Prodeus, A. P., Zhou, X., Maurer, M., Galli, S. J. & Carroll, M. C. Impaired mast cell-dependent natural immunity in complement C3-deficient mice. Nature 390, 172–175 (1997).
Lora, J. M. et al. FcεRI-dependent gene expression in human mast cells is differentially controlled by T helper type 2 cytokines. J. Allergy Clin. Immunol. 112, 1119–1126 (2003).
Ochi, H., De Jesus, N. H., Hsieh, F. H., Austen, K. F. & Boyce, J. A. IL-4 and -5 prime human mast cells for different profiles of IgE-dependent cytokine production. Proc. Natl Acad. Sci. USA 97, 10509–10513 (2000).
Hsieh, F. H., Lam, B. K., Penrose, J. F., Austen, K. F. & Boyce, J. A. T helper cell type 2 cytokines coordinately regulate immunoglobulin E-dependent cysteinyl leukotriene production by human cord blood-derived mast cells: profound induction of leukotriene C4 synthase expression by interleukin 4. J. Exp. Med. 193, 123–133 (2001).
Bischoff, S. C., Sellge, G., Manns, M. P. & Lorentz, A. Interleukin-4 induces a switch of human intestinal mast cells from proinflammatory cells to TH2-type cells. Int. Arch. Allergy Immunol. 124, 151–154 (2001).
Kandere-Grzybowska, K. et al. IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells. J. Immunol. 171, 4830–4836 (2003).
Leal-Berumen, I., O'Byrne, P., Gupta, A., Richards, C. D. & Marshall, J. S. Prostanoid enhancement of interleukin-6 production by rat peritoneal mast cells. J. Immunol. 154, 4759–4767 (1995).
Abdel-Majid, R. M. & Marshall, J. S. Prostaglandin E2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells. J. Immunol. 172, 1227–1236 (2004).
Mellor, E. A., Austen, K. F. & Boyce, J. A. Cysteinyl leukotrienes and uridine diphosphate induce cytokine generation by human mast cells through an interleukin 4-regulated pathway that is inhibited by leukotriene receptor antagonists. J. Exp. Med. 195, 583–592 (2002). This report was the first to show that cysteinyl leukotrienes can activate human mast cells to selectively produce cytokines.
Figueroa, D. J. et al. Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis. Clin. Exp. Allergy 33, 1380–1388 (2003).
Mellor, E. A. et al. Expression of the type 2 receptor for cysteinyl leukotrienes (CysLT2R) by human mast cells: functional distinction from CysLT1R. Proc. Natl Acad. Sci. USA 100, 11589–11593 (2003).
Leal-Berumen, I., Snider, D. P., Barajas-Lopez, C. & Marshall, J. S. Cholera toxin increases IL-6 synthesis and decreases TNF-α production by rat peritoneal mast cells. J. Immunol. 156, 316–321 (1996).
King, C. A., Anderson, R. & Marshall, J. S. Dengue virus selectively induces human mast cell chemokine production. J. Virol. 76, 8408–8419 (2002). This paper was the first to show the selective production of chemokines by mast cells as a result of viral infection, which has implications for the pathogenesis of dengue-virus-induced disease.
Lin, T. J., Garduno, R., Boudreau, R. T. & Issekutz, A. C. Pseudomonas aeruginosa activates human mast cells to induce neutrophil transendothelial migration via mast cell-derived IL-1α and β. J. Immunol. 169, 4522–4530 (2002).
Lin, T. J. et al. Selective early production of CCL20, or macrophage inflammatory protein 3α, by human mast cells in response to Pseudomonas aeruginosa. Infect. Immun. 71, 365–373 (2003).
King, C. A., Marshall, J. S., Alshurafa, H. & Anderson, R. Release of vasoactive cytokines by antibody enhanced dengue virus infection of a human mast cell/basophil line. J. Virol. 74, 7146–7150 (2000).
Malaviya, R. & Abraham, S. N. Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis. J. Leukoc. Biol. 67, 841–846 (2000).
Tani, K. et al. Chymase is a potent chemoattractant for human monocytes and neutrophils. J. Leukoc. Biol. 67, 585–589 (2000).
Huang, C. et al. Evaluation of the substrate specificity of human mast cell tryptase βI and demonstration of its importance in bacterial infections of the lung. J. Biol. Chem. 276, 26276–26284 (2001).
Vergnolle, N. Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J. Immunol. 163, 5064–5069 (1999).
Lindner, J. R. et al. Delayed onset of inflammation in protease-activated receptor-2-deficient mice. J. Immunol. 165, 6504–6510 (2000).
Williams, C. M. & Coleman, J. W. Induced expression of mRNA for IL-5, IL-6, TNF-α, MIP-2 and IFN-γ in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A. Immunology 86, 244–249 (1995).
Babina, M. et al. Comparative cytokine profile of human skin mast cells from two compartments — strong resemblance with monocytes at baseline but induction of IL-5 by IL-4 priming. J. Leukoc. Biol. 75, 244–252 (2003).
Hogaboam, C. et al. Novel role of transmembrane SCF for mast cell activation and eotaxin production in mast cell–fibroblast interactions. J. Immunol. 160, 6166–6171 (1998).
Rajakulasingam, K. et al. RANTES in human allergen-induced rhinitis: cellular source and relation to tissue eosinophilia. Am. J. Respir. Crit. Care Med. 155, 696–703 (1997).
Donaldson, L. E., Schmitt, E., Huntley, J. F., Newlands, G. F. & Grencis, R. K. A critical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth. Int. Immunol. 8, 559–567 (1996).
Grencis, R. K. TH2-mediated host protective immunity to intestinal nematode infections. Phil. Trans. R. Soc. Lond. B 352, 1377–1384 (1997).
Ott, V. L., Cambier, J. C., Kappler, J., Marrack, P. & Swanson, B. J. Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4 . Nature Immunol. 4, 974–981 (2003). This report showed the importance of mast-cell-derived LTB 4 as a chemoattractant for CD8+ effector T cells.
Malaviya, R., Twesten, N. J., Ross, E. A., Abraham, S. N. & Pfeifer, J. D. Mast cells process bacterial Ags through a phagocytic route for class I MHC presentation to T cells. J. Immunol. 156, 1490–1496 (1996).
Poncet, P., Arock, M. & David, B. MHC class II-dependent activation of CD4+ T cell hybridomas by human mast cells through superantigen presentation. J. Leukoc. Biol. 66, 105–112 (1999).
Frandji, P. et al. Exogenous and endogenous antigens are differentially presented by mast cells to CD4+ T lymphocytes. Eur. J. Immunol. 26, 2517–2528 (1996).
Mazzoni, A., Young, H. A., Spitzer, J. H., Visintin, A. & Segal, D. M. Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization. J. Clin. Invest. 108, 1865–1873 (2001).
Mazzoni, A. et al. Histamine inhibits IFN-α release from plasmacytoid dendritic cells. J. Immunol. 170, 2269–2273 (2003).
Skokos, D. et al. Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J. Immunol. 170, 3037–3045 (2003).
McLachlan, J. B. et al. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nature Immunol. 4, 1199–1205 (2003). This paper was the first to show that mast cells have an important role in the regulation of lymph-node hypertrophy during infection, using a TNF-dependent mechanism.
Gordon, J. R. & Galli, S. J. Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin. Nature 346, 274–276 (1990). This was the first formal proof that mast cells can release pre-formed TNF, which is crucial for early innate immune responses, as well as important in the generation of a longer-term response to TNF.
Finkelman, F. D. & Urban, J. F. Jr. The other side of the coin: the protective role of the TH2 cytokines. J. Allergy Clin. Immunol. 107, 772–780 (2001).
Woodbury, R. G. et al. Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat. Nature 312, 450–452 (1984). This was the first report to show that activation of mucosal mast cells and the release of proteases are temporally associated with nematode expulsion.
Lantz, C. S. et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392, 90–93 (1998).
Mahida, Y. R. Host-parasite interactions in rodent nematode infections. J. Helminthol. 77, 125–131 (2003).
Henz, B. M., Maurer, M., Lippert, U., Worm, M. & Babina, M. Mast cells as initiators of immunity and host defense. Exp. Dermatol. 10, 1–10 (2001).
Wershil, B. K., Theodos, C. M., Galli, S. J. & Titus, R. G. Mast cells augment lesion size and persistence during experimental Leishmania major infection in the mouse. J. Immunol. 152, 4563–4571 (1994).
Faulkner, H., Renauld, J. C., Van Snick J. & Grencis, R. K. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect. Immun. 66, 3832–3840 (1998).
McDermott, J. R. et al. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc. Natl Acad. Sci. USA 100, 7761–7766 (2003). This paper showed the crucial role of mast cells and mast-cell proteases in disruption of the epithelial barrier to mediate the expulsion of nematodes.
Cutts, L. & Wilson, R. A. Elimination of a primary schistosome infection from rats coincides with elevated IgE titres and mast cell degranulation. Parasite Immunol. 19, 91–102 (1997).
Bleiss, W. et al. Protective immunity induced by irradiated third-stage larvae of the filaria Acanthocheilonema viteae is directed against challenge third-stage larvae before molting. J. Parasitol. 88, 264–270 (2002).
Malaviya, R. & Abraham, S. N. Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis. J. Leukoc. Biol. 67, 841–846 (2000).
Gommerman, J. L. et al. A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: a potential mechanism for mast cell activation. J. Immunol. 165, 6915–6921 (2000).
Edelson, B. T., Li, Z., Pappan, L. K. & Zutter, M. M. Mast cell-mediated inflammatory responses require the α2β1 integrin. Blood 103, 2214–2220 (2004).
Maurer, M. et al. The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells. J. Exp. Med. 188, 2343–2348 (1998).
Li, Y. et al. Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4. Blood 97, 3484–3490 (2001).
Bannert, N. et al. Human mast cell progenitors can be infected by macrophagetropic human immunodeficiency virus type 1 and retain virus with maturation in vitro. J. Virol. 75, 10808–10814 (2001).
Gibbons, A. E., Price, P., Robertson, T. A., Padimitriou, J. M. & Shellam, G. R. Replication of murine cytomegalovirus in mast cells. Arch. Virol. 115, 299–307 (1990).
Sundstrom, J. B., Little, D. M., Villinger, F., Ellis, J. E. & Ansari, A. A. Signaling through Toll-like receptors triggers HIV-1 replication in latently infected mast cells. J. Immunol. 172, 4391–4401 (2004).
Kimman, T. G., Terpstra, G. K., Daha, M. R. & Westenbrink, F. Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: evidence for the involvement of complement and mast cell mediators. Am. J. Vet. Res. 50, 694–700 (1989).
van Schaik, S. M. et al. Increased production of IFN-γ and cysteinyl leukotrienes in virus-induced wheezing. J. Allergy Clin. Immunol. 103, 630–636 (1999).
Castleman, W. L., Sorkness, R. L., Lemanske, R. F. Jr & McAllister, P. K. Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness. Am. J. Pathol. 137, 821–831 (1990).
Mokhtarian, F. & Griffin, D. E. The role of mast cells in virus-induced inflammation in the murine central nervous system. Cell. Immunol. 86, 491–500 (1984).
Sorden, S. D. & Castleman, W. L. Virus-induced increases in airway mast cells in Brown Norway rats are associated with enhanced pulmonary viral replication and persisting lymphocytic infiltration. Exp. Lung Res. 21, 197–213 (1995).
Bridges, A. J. et al. Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy. Arthritis Rheum. 34, 1116–1124 (1991).
Johnston, B., Burns, A. R. & Kubes, P. A role for mast cells in the development of adjuvant-induced vasculitis and arthritis. Am. J. Pathol. 152, 555–563 (1998).
Lee, D. M. et al. Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297, 1689–1692 (2002).
Kaartinen, M., Penttila, A. & Kovanen, P. T. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-α. Circulation 94, 2787–2792 (1996).
Kaartinen, M., Penttila, A. & Kovanen, P. T. Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage. Atherosclerosis 123, 123–131 (1996).
Masenga, J., Garbe, C., Wagner, J. & Orfanos, C. E. Staphylococcus aureus in atopic dermatitis and in nonatopic dermatitis. Int. J. Dermatol. 29, 579–582 (1990).
Abeck, D. & Mempel, M. Staphylococcus aureus colonization in atopic dermatitis and its therapeutic implications. Br. J. Dermatol. 139 (Suppl. 53), 13–16 (1998).
Razin, E. et al. IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, β-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells. J. Exp. Med. 157, 189–201 (1983).
Vensel, W. H., Komender, J. & Barnard, E. A. Non-pancreatic proteases of the chymotrypsin family. II. Two proteases from a mouse mast cell tumor. Biochim. Biophys. Acta 250, 395–407 (1971).
Ochi, H. et al. T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J. Exp. Med. 190, 267–280 (1999).
Woodbury, R. G. & Neurath, H. Purification of an atypical mast cell protease and its levels in developing rats. Biochemistry 17, 4298–4304 (1978).
Boesiger, J. et al. Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of Fcε receptor I expression. J. Exp. Med. 188, 1135–1145 (1998).
Qu, Z. et al. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am. J. Pathol. 147, 564–573 (1995).
Reed, J. A., Albino, A. P. & McNutt, N. S. Human cutaneous mast cells express basic fibroblast growth factor. Lab. Invest. 72, 215–222 (1995).
Razin, E., Mencia-Huerta, J. M., Lewis, R. A., Corey, E. J. & Austen, K. F. Generation of leukotriene C4 from a subclass of mast cells differentiated in vitro from mouse bone marrow. Proc. Natl Acad. Sci. USA 79, 4665–4667 (1982).
Freeland, H. S., Schleimer, R. P., Schulman, E. S., Lichtenstein, L. M. & Peters, S. P. Generation of leukotriene B4 by human lung fragments and purified human lung mast cells. Am. Rev. Respir. Dis. 138, 389–394 (1988).
Marshall, J. S., Gomi, K., Blennerhassett, M. G. & Bienenstock, J. Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J. Immunol. 162, 4271–4276 (1999).
Mencia-Huerta, J. M., Lewis, R. A., Razin, E. & Austen, K. F. Antigen-initiated release of platelet-activating factor (PAF-acether) from mouse bone marrow-derived mast cells sensitized with monoclonal IgE. J. Immunol. 131, 2958–2964 (1983).
Plaut, M. et al. Mast cell lines produce lymphokines in response to cross-linkage of FcεRI or to calcium ionophores. Nature 339, 64–67 (1989).
Burd, P. R. et al. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J. Exp. Med. 170, 245–257 (1989). References 139 and 140 were the first reports to show that mast cells can produce multiple cytokines, thereby opening up the possibility that these cells have a wider role in host defence than that previously envisaged.
Gordon, J. R., Burd, P. R. & Galli, S. J. Mast cells as a source of multifunctional cytokines. Immunol. Today 11, 458–464 (1990).
Marshall, J. S., Gauldie, J., Nielsen, L. & Bienenstock, J. Leukemia inhibitory factor production by rat mast cells. Eur. J. Immunol. 23, 2116–2120 (1993).
Stassen, M. et al. IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide: NF-κB is decisively involved in the expression of IL-9. J. Immunol. 166, 4391–4398 (2001).
Rumsaeng, V. et al. Human mast cells produce the CD4+ T lymphocyte chemoattractant factor, IL-16. J. Immunol. 159, 2904–2910 (1997).
Smith, T. J., Ducharme, L. A. & Weis, J. H. Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow mast cells derived in mast cell growth factor or interleukin-3. Eur. J. Immunol. 24, 822–826 (1994).
Bissonnette, E. Y., Enciso, J. A. & Befus, A. D. TGF-β1 inhibits the release of histamine and tumor necrosis factor-α from mast cells through an autocrine pathway. Am. J. Respir. Cell Mol. Biol. 16, 275–282 (1997).
Selvan, R. S., Butterfield, J. H. & Krangel, M. S. Expression of multiple chemokine genes by a human mast cell leukemia. J. Biol. Chem. 269, 13893–13898 (1994).
Jia, G. Q. et al. Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation. J. Exp. Med. 184, 1939–1951 (1996).
Moller, A. et al. Human mast cells produce IL-8. J. Immunol. 151, 3261–3266 (1993).
Mori, Y. et al. Tyk2 is essential for IFN-α-induced gene expression in mast cells. Int. Arch. Allergy Immunol. 134 (Suppl. 1), 25–29 (2004).
Bissonnette, E. Y., Hogaboam, C. M., Wallace, J. L. & Befus, A. D. Potentiation of tumor necrosis factor-α-mediated cytotoxicity of mast cells by their production of nitric oxide. J. Immunol. 147, 3060–3065 (1991).
Gilchrist, M., McCauley, S. D. & Befus, A. D. Expression, localization and regulation of nitric oxide synthase (NOS) in human mast cell lines: effects on leukotriene production. Blood 104, 462–469 (2004).
Malaviya, R. et al. Mast cell phagocytosis of FimH-expressing enterobacteria. J. Immunol. 152, 1907–1914 (1994).
Applequist, S. E., Wallin, R. P. & Ljunggren, H. G. Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines. Int. Immunol. 14, 1065–1074 (2002).
Munoz, S., Hernandez-Pando, R., Abraham, S. N. & Enciso, J. A. Mast cell activation by Mycobacterium tuberculosis: mediator release and role of CD48. J. Immunol. 170, 5590–5596 (2003).
Segal, D. M., Taurog, J. D. & Metzger, H. Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Proc. Natl Acad. Sci. USA 74, 2993–2997 (1977).
Sher, A., Hein, A., Moser, G. & Caulfield, J. P. Complement receptors promote the phagocytosis of bacteria by rat peritoneal mast cells. Lab. Invest. 41, 490–499 (1979).
Andrasfalvy, M., Prechl, J., Hardy, T., Erdei, A. & Bajtay, Z. Mucosal type mast cells express complement receptor type 2 (CD21). Immunol. Lett. 82, 29–34 (2002).
Schulman, E. S., Post, T. J., Henson, P. M. & Giclas, P. C. Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release. J. Clin. Invest. 81, 918–923 (1988).
el-Lati, S. G., Dahinden, C. A. & Church, M. K. Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J. Invest. Dermatol. 102, 803–806 (1994).
Hartmann, K. et al. C3a and C5a stimulate chemotaxis of human mast cells. Blood 89, 2863–2870 (1997).
Stenton, G. R. et al. Proteinase-activated receptor (PAR)-1 and -2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 and PAR-2. J. Pharmacol. Exp. Ther. 302, 466–474 (2002).
Love, K. S., Lakshmanan, R. R., Butterfield, J. H. & Fox, C. C. IFN-γ-stimulated enhancement of MHC class II antigen expression by the human mast cell line HMC-1. Cell Immunol. 170, 85–90 (1996).
Lin, T. J. & Befus, A. D. Differential regulation of mast cell function by IL-10 and stem cell factor. J. Immunol. 159, 4015–4023 (1997).
Lin, T. J., Issekutz, T. B. & Marshall, J. S. Human mast cells transmigrate through human umbilical vein endothelial monolayers and selectively produce IL-8 in response to stromal cell-derived factor-1α. J. Immunol. 165, 211–220 (2000).
Malaviya, R., Ikeda, T. & Abraham, S. N. Contribution of mast cells to bacterial clearance and their proliferation during experimental cystitis induced by type 1 fimbriated E. coli. Immunol. Lett. 91, 103–111 (2004).
Sorden, S. D. & Castleman, W. L. Virus-induced increases in bronchiolar mast cells in Brown Norway rats are associated with both local mast cell proliferation and increases in blood mast cell precursors. Lab. Invest. 73, 197–204 (1995).
Jolly, S., Detilleux, J. & Desmecht, D. Extensive mast cell degranulation in bovine respiratory syncytial virus-associated paroxystic respiratory distress syndrome. Vet. Immunol. Immunopathol. 97, 125–136 (2004).
Miller, H. R., Woodbury, R. G., Huntley, J. F. & Newlands, G. Systemic release of mucosal mast-cell protease in primed rats challenged with Nippostrongylus brasiliensis. Immunology 49, 471–479 (1983).
Matsuda, H., Fukui, K., Kiso, Y. & Kitamura, Y. Inability of genetically mast cell-deficient W/Wv mice to acquire resistance against larval Haemaphysalis longicornis ticks. J. Parasitol. 71, 443–448 (1985).
Nawa, Y., Kiyota, M., Korenaga, M. & Kotani, M. Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells. Parasite Immunol. 7, 429–438 (1985).
Ha, T. Y., Reed, N. D. & Crowle, P. K. Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice. Infect. Immun. 41, 445–447 (1983).
Knight, P. A., Wright, S. H., Lawrence, C. E., Paterson, Y. Y. & Miller, H. R. Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1. J. Exp. Med. 192, 1849–1856 (2000).
Abe, T. & Nawa, Y. Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice. Immunology 63, 181–185 (1988).
The author declares no competing financial interests.
- POLYBASIC COMPOUNDS
Compounds that contain repeats of negatively charged units, such as compound 48/80 and magainin.
- DISODIUM CROMOGLYCATE
A frequently used mast-cell stabilizing agent that prevents degranulation of certain types of mast cell in response to IgE-mediated activation.
The development of new blood vessels from existing blood vessels. It is frequently associated with tumour development and inflammation.
An agent that induces constriction of airway smooth muscle and thereby reduces the capacity for air-flow in the main airways.
A member of the chemokine family in which the first two amino-terminal cysteine residues are adjacent.
A member of the chemokine family in which the first two amino-terminal cysteine residues are separated by an intervening amino acid.
- B-CELL SUPERANTIGENS
Substances that induce activation of some cells that express cell-surface immunoglobulin, through binding that is independent of the antigen specificity of the immunoglobulin.
- CAECAL LIGATION AND PUNCTURE
An experimental model of peritonitis in rodents, in which the caecum is ligated and then punctured, thereby forming a small hole. This leads to leakage of intestinal bacteria into the peritoneal cavity and subsequent peritoneal infection.
- DENGUE VIRUS
A member of the dengue group of RNA viruses that cause dengue fever.
- ANTIBODY-ENHANCED INFECTION
A viral infection that is enhanced by the presence of subneutralizing concentrations of virus-specific antibody.
Small lipid-bilayer vesicles that are released from activated cells. They comprise either plasma membrane or membrane derived from intracellular vesicles.
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Marshall, J. Mast-cell responses to pathogens. Nat Rev Immunol 4, 787–799 (2004). https://doi.org/10.1038/nri1460
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