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Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking

Leukemia volume 24, pages 1993–2002 (2010)Cite this article

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Abstract

Hematopoietic stem cell (HSC) transplantation is a potentially curative treatment for numerous hematological malignancies. The transplant procedure as performed today takes advantage of HSC trafficking; either egress of HSC from the bone marrow to the peripheral blood, that is, mobilization, for acquisition of the hematopoietic graft, and/or trafficking of HSC from the peripheral blood to bone marrow niches in the recipient patient, that is HSC homing. Numerous studies, many of which are reviewed herein, have defined hematopoietic regulatory mechanisms mediated by the 20-carbon lipid family of eicosanoids, and recent evidence strongly supports a role for eicosanoids in regulation of hematopoietic trafficking, adding a new role whereby eicosanoids regulate hematopoiesis. Short-term exposure of HSC to the eicosanoid prostaglandin E2 increases CXCR4 receptor expression, migration and in vivo homing of HSC. In contrast, cannabinoids reduce hematopoietic progenitor cell (HPC) CXCR4 expression and induce HPC mobilization when administered in vivo. Leukotrienes have been shown to alter CD34+ cell adhesion, migration and regulate HSC proliferation, suggesting that eicosanoids have both opposing and complimentary roles in the regulation of hematopoiesis. As numerous FDA approved compounds regulate eicosanoid signaling or biosynthesis, the utility of eicosanoid-based therapeutic strategies to improve hematopoietic transplantation can be rapidly evaluated.

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References

  1. Bhattacharya D, Czechowicz A, Ooi AG, Rossi DJ, Bryder D, Weissman IL . Niche recycling through division-independent egress of hematopoietic stem cells. J Exp Med 2009; 206: 2837–2850.

    CAS  Google Scholar 

  2. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL . Physiological migration of hematopoietic stem and progenitor cells. Science 2001; 294: 1933–1936.

    Article  CAS  Google Scholar 

  3. Abkowitz JL, Robinson AE, Kale S, Long MW, Chen J . Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 2003; 102: 1249–1253.

    CAS  Google Scholar 

  4. Nibley WE, Spangrude GJ . Primitive stem cells alone mediate rapid marrow recovery and multilineage engraftment after transplantation. Bone Marrow Transplant 1998; 21: 345–354.

    CAS  Google Scholar 

  5. Lanzkron SM, Collector MI, Sharkis SJ . Homing of long-term and short-term engrafting cells in vivo. Ann N Y Acad Sci 1999; 872: 48–54.

    CAS  Google Scholar 

  6. Vose JM, Ho AD, Coiffier B, Corradini P, Khouri I, Sureda A et al. Advances in mobilization for the optimization of autologous stem cell transplantation. Leuk Lymphoma 2009; 50: 1412–1421.

    CAS  Google Scholar 

  7. Moog R . Management strategies for poor peripheral blood stem cell mobilization. Transfus Apher Sci 2008; 38: 229–236.

    Google Scholar 

  8. Broxmeyer HE . Umbilical cord transplantation: epilogue. Semin Hematol 2010; 47: 97–103.

    Google Scholar 

  9. Hall KM, Horvath TL, Abonour R, Cornetta K, Srour EF . Decreased homing of retrovirally transduced human bone marrow CD34+ cells in the NOD/SCID mouse model. Exp Hematol 2006; 34: 433–442.

    CAS  Google Scholar 

  10. Broxmeyer HE . Cord Blood Hematopoietic Stem and Progenitor Cells. Essentials of Stem Cell Biology. Elsevier, Inc: St Louis, MO 2006, pp 133–137.

  11. Porecha NK, English K, Hangoc G, Broxmeyer HE, Christopherson KW . Enhanced functional response to CXCL12/SDF-1 through retroviral overexpression of CXCR4 on M07e cells: implications for hematopoietic stem cell transplantation. Stem Cells Dev 2006; 15: 325–333.

    CAS  Google Scholar 

  12. Funk CD . Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001; 294: 1871–1875.

    CAS  Google Scholar 

  13. Legler DF, Bruckner M, Uetz-von AE, Krause P . Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol 2010; 42: 198–201.

    CAS  Google Scholar 

  14. Miller SB . Prostaglandins in health and disease: an overview. Semin Arthritis Rheum 2006; 36: 37–49.

    CAS  Google Scholar 

  15. Ivanov AI, Romanovsky AA . Prostaglandin E2 as a mediator of fever: synthesis and catabolism. Front Biosci 2004; 9: 1977–1993.

    CAS  Google Scholar 

  16. Murakami M, Kudo I . Prostaglandin E synthase: a novel drug target for inflammation and cancer. Curr Pharm Des 2006; 12: 943–954.

    CAS  Google Scholar 

  17. Park JY, Pillinger MH, Abramson SB . Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol 2006; 119: 229–240.

    CAS  Google Scholar 

  18. Mitchell JA, Warner TD . COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat Rev Drug Discov 2006; 5: 75–86.

    CAS  Google Scholar 

  19. Strand V . Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007; 370: 2138–2151.

    CAS  Google Scholar 

  20. Coruzzi G, Venturi N, Spaggiari S . Gastrointestinal safety of novel nonsteroidal antiinflammatory drugs: selective COX-2 inhibitors and beyond. Acta Biomed 2007; 78: 96–110.

    CAS  Google Scholar 

  21. Tsuboi K, Sugimoto Y, Ichikawa A . Prostanoid receptor subtypes. Prostaglandins Other Lipid Mediat 2002; 68-69: 535–556.

    CAS  Google Scholar 

  22. Miyaura C, Inada M, Matsumoto C, Ohshiba T, Uozumi N, Shimizu T et al. An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 2003; 197: 1303–1310.

    CAS  Google Scholar 

  23. Chen QR, Miyaura C, Higashi S, Murakami M, Kudo I, Saito S et al. Activation of cytosolic phospholipase A2 by platelet-derived growth factor is essential for cyclooxygenase-2-dependent prostaglandin E2 synthesis in mouse osteoblasts cultured with interleukin-1. J Biol Chem 1997; 272: 5952–5958.

    CAS  Google Scholar 

  24. Raisz LG, Vanderhoek JY, Simmons HA, Kream BE, Nicolaou KC . Prostaglandin synthesis by fetal rat bone in vitro: evidence for a role of prostacyclin. Prostaglandins 1979; 17: 905–914.

    CAS  Google Scholar 

  25. Pelus LM, Broxmeyer HE, Kurland JI, Moore MA . Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin. J Exp Med 1979; 150: 277–292.

    CAS  Google Scholar 

  26. Pelus LM, Broxmeyer HE, Moore MA . Regulation of human myelopoiesis by prostaglandin E and lactoferrin. Cell Tissue Kinet 1981; 14: 515–526.

    CAS  Google Scholar 

  27. Kurland JI, Pelus LM, Ralph P, Bockman RS, Moore MA . Induction of prostaglandin E synthesis in normal and neoplastic macrophages: role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation. Proc Natl Acad Sci USA 1979; 76: 2326–2330.

    CAS  Google Scholar 

  28. Steinhilber D . 5-Lipoxygenase: a target for antiinflammatory drugs revisited. Curr Med Chem 1999; 6: 71–85.

    CAS  Google Scholar 

  29. Serhan CN, Sheppard KA . Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J Clin Invest 1990; 85: 772–780.

    CAS  Google Scholar 

  30. Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 2003; 21: 759–806.

    CAS  Google Scholar 

  31. Kim N, Luster AD . Regulation of immune cells by eicosanoid receptors. ScientificWorldJournal 2007; 7: 1307–1328.

    CAS  Google Scholar 

  32. Ligresti A, Cascio MG, Di MV . Endocannabinoid metabolic pathways and enzymes. Curr Drug Targets CNS Neurol Disord 2005; 4: 615–623.

    CAS  Google Scholar 

  33. Malcher-Lopes R, Franco A, Tasker JG . Glucocorticoids shift arachidonic acid metabolism toward endocannabinoid synthesis: a non-genomic anti-inflammatory switch. Eur J Pharmacol 2008; 583: 322–339.

    CAS  Google Scholar 

  34. Okamoto Y, Wang J, Morishita J, Ueda N . Biosynthetic pathways of the endocannabinoid anandamide. Chem Biodivers 2007; 4: 1842–1857.

    CAS  Google Scholar 

  35. Kozak KR, Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 2002; 277: 44877–44885.

    CAS  Google Scholar 

  36. Weber A, Ni J, Ling KH, Acheampong A, Tang-Liu DD, Burk R et al. Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry. J Lipid Res 2004; 45: 757–763.

    CAS  Google Scholar 

  37. Yu M, Ives D, Ramesha CS . Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem 1997; 272: 21181–21186.

    CAS  Google Scholar 

  38. Kozak KR, Crews BC, Ray JL, Tai HH, Morrow JD, Marnett LJ . Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in vitro and in vivo. J Biol Chem 2001; 276: 36993–36998.

    CAS  Google Scholar 

  39. Wang J, Ueda N . Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat 2009; 89: 112–119.

    CAS  Google Scholar 

  40. Placzek EA, Okamoto Y, Ueda N, Barker EL . Mechanisms for recycling and biosynthesis of endogenous cannabinoids anandamide and 2-arachidonylglycerol. J Neurochem 2008; 107: 987–1000.

    CAS  Google Scholar 

  41. Mitchell MD, Sato TA, Wang A, Keelan JA, Ponnampalam AP, Glass M . Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue- and CB1-receptor-specific mechanism. Am J Physiol Endocrinol Metab 2008; 294: E352–E356.

    CAS  Google Scholar 

  42. Konger RL, Brouxhon S, Partillo S, VanBuskirk J, Pentland AP . The EP3 receptor stimulates ceramide and diacylglycerol release and inhibits growth of primary keratinocytes. Exp Dermatol 2005; 14: 914–922.

    CAS  Google Scholar 

  43. Aglietta M, Piacibello W, Gavosto F . Insensitivity of chronic myeloid leukemia cells to inhibition of growth by prostaglandin E1. Cancer Res 1980; 40: 2507–2511.

    CAS  Google Scholar 

  44. Pelus LM, Broxmeyer HE, Clarkson BD, Moore MA . Abnormal responsiveness of granulocyte-macrophage committed colony-forming cells from patients with chronic myeloid leukemia to inhibition by prostaglandin E1. Cancer Res 1980; 40: 2512–2515.

    CAS  Google Scholar 

  45. Taetle R, Guittard JP, Mendelsohn JM . Abnormal modulation of granulocyte/macrophage progenitor proliferation by prostaglandin E in chronic myeloproliferative disorders. Exp Hematol 1980; 8: 1190–1201.

    CAS  Google Scholar 

  46. Taetle R, Koessler A . Effects of cyclic nucleotides and prostaglandins on normal and abnormal human myeloid progenitor proliferation. Cancer Res 1980; 40: 1223–1229.

    CAS  Google Scholar 

  47. Kincade PW, Lee G, Fernandes G, Moore MA, Williams N, Good RA . Abnormalities in clonable B lymphocytes and myeloid progenitors in autoimmune NZB mice. Proc Natl Acad Sci USA 1979; 76: 3464–3468.

    CAS  Google Scholar 

  48. Pelus LM, Gold E, Saletan S, Coleman M . Restoration of responsiveness of chronic myeloid leukemia granulocyte-macrophage colony-forming cells to growth regulation in vitro following preincubation with prostaglandin E. Blood 1983; 62: 158–165.

    CAS  Google Scholar 

  49. Moore MA, Mertelsmann R, Pelus LM . Phenotypic evaluation of chronic myeloid leukemia. Blood Cells 1981; 7: 217–236.

    CAS  Google Scholar 

  50. Gold EJ, Conjalka M, Pelus LM, Jhanwar SC, Broxmeyer H, Middleton AB et al. Marrow cytogenetic and cell-culture analyses of the myelodysplastic syndromes: insights to pathophysiology and prognosis. J Clin Oncol 1983; 1: 627–634.

    CAS  Google Scholar 

  51. Leitner SP, Bosl GJ, Pelus LM . Abnormal colony formation and prostaglandin E responsiveness of myeloid progenitor cells in patients cured of germ cell neoplasms after combination chemotherapy. Cancer 1987; 60: 312–317.

    CAS  Google Scholar 

  52. Pelus LM, Vadhan-Raj S . Modulation of responsiveness of chronic myelogenous leukemia granulocyte-macrophage colony-forming cells to growth regulation following in vivo treatment with recombinant gamma-interferon. Am J Hematol 1988; 28: 21–26.

    CAS  Google Scholar 

  53. Vadhan-Raj S, Al Katib A, Bhalla R, Pelus L, Nathan CF, Sherwin SA et al. Phase I trial of recombinant interferon gamma in cancer patients. J Clin Oncol 1986; 4: 137–146.

    CAS  Google Scholar 

  54. Feher I, Gidali J . Prostaglandin E2 as stimulator of haemopoietic stem cell proliferation. Nature 1974; 247: 550–551.

    CAS  Google Scholar 

  55. Verma DS, Spitzer G, Zander AR, McCredie KB, Dicke KA . Prostaglandin E1-mediated augmentation of human granulocyte-macrophage progenitor cell growth in vitro. Leuk Res 1981; 5: 65–71.

    CAS  Google Scholar 

  56. Gidali J, Feher I . The effect of E type prostaglandins on the proliferation of haemopoietic stem cells in vivo. Cell Tissue Kinet 1977; 10: 365–373.

    CAS  Google Scholar 

  57. Gentile PS, Byer D, Pelus LM . In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2. Blood 1983; 62: 1100–1107.

    CAS  Google Scholar 

  58. Gentile PS, Pelus LM . In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of granulocyte-monocyte progenitor cell (CFU-GM) cell-cycle rate. Exp Hematol 1987; 15: 119–126.

    CAS  Google Scholar 

  59. Gentile PS, Pelus LM . In vivo modulation of myelopoiesis by prostaglandin E2. IV. Prostaglandin E2 induction of myelopoietic inhibitory activity. J Immunol 1988; 141: 2714–2720.

    CAS  Google Scholar 

  60. Pelus LM, Gentile PS . In vivo modulation of myelopoiesis by prostaglandin E2. III. Induction of suppressor cells in marrow and spleen capable of mediating inhibition of CFU-GM proliferation. Blood 1988; 71: 1633–1640.

    CAS  Google Scholar 

  61. Pelus LM . CFU-GM expression of Ia-like, HLA-DR, antigen: an association with the humoral control of human granulocyte and macrophage production. Exp Hematol 1982; 10: 219–231.

    Google Scholar 

  62. Pelus LM . Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E. J Clin Invest 1982; 70: 568–578.

    CAS  Google Scholar 

  63. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 2007; 447: 1007–1011.

    CAS  Google Scholar 

  64. Malhotra S, Kincade PW . Wnt-related molecules and signaling pathway equilibrium in hematopoiesis. Cell Stem Cell 2009; 4: 27–36.

    CAS  Google Scholar 

  65. Regan JW . EP2 and EP4 prostanoid receptor signaling. Life Sci 2003; 74: 143–153.

    CAS  Google Scholar 

  66. Wang D, Mann JR, DuBois RN . WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. Cell Cycle 2004; 3: 1512–1515.

    CAS  Google Scholar 

  67. Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009; 136: 1136–1147.

    CAS  Google Scholar 

  68. Hoggatt J, Singh P, Sampath J, Pelus LM . Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood 2009; 113: 5444–5455.

    CAS  Google Scholar 

  69. Fukuda S, Foster RG, Porter SB, Pelus LM . The antiapoptosis protein survivin is associated with cell cycle entry of normal cord blood CD34(+) cells and modulates cell cycle and proliferation of mouse hematopoietic progenitor cells. Blood 2002; 100: 2463–2471.

    CAS  Google Scholar 

  70. Fukuda S, Pelus LM . Elevation of Survivin levels by hematopoietic growth factors occurs in quiescent CD34+ hematopoietic stem and progenitor cells before cell cycle entry. Cell Cycle 2002; 1: 322–326.

    CAS  Google Scholar 

  71. Frisch BJ, Porter RL, Gigliotti BJ, Olm-Shipman AJ, Weber JM, O’Keefe RJ et al. In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells. Blood 2009; 114: 4054–4063.

    CAS  Google Scholar 

  72. Croxford JL, Yamamura T . Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol 2005; 166: 3–18.

    CAS  Google Scholar 

  73. Klein TW, Lane B, Newton CA, Friedman H . The cannabinoid system and cytokine network. Proc Soc Exp Biol Med 2000; 225: 1–8.

    CAS  Google Scholar 

  74. Valk PJ, Verbakel S, Vankan Y, Hol S, Mancham S, Ploemacher R et al. Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood 1997; 90: 1448–1457.

    CAS  Google Scholar 

  75. Bentzen PJ, Lang F . Effect of anandamide on erythrocyte survival. Cell Physiol Biochem 2007; 20: 1033–1042.

    CAS  Google Scholar 

  76. Valk PJ, Delwel R . The peripheral cannabinoid receptor, Cb2, in retrovirally-induced leukemic transformation and normal hematopoiesis. Leuk Lymphoma 1998; 32: 29–43.

    CAS  Google Scholar 

  77. Patinkin D, Milman G, Breuer A, Fride E, Mechoulam R . Endocannabinoids as positive or negative factors in hematopoietic cell migration and differentiation. Eur J Pharmacol 2008; 595: 1–6.

    CAS  Google Scholar 

  78. Jiang S, Fu Y, Williams J, Wood J, Pandarinathan L, Avraham S et al. Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS One 2007; 2: e641.

    Google Scholar 

  79. Rayman N, Lam KH, Van LJ, Mulder AH, Budel LM, Lowenberg B et al. The expression of the peripheral cannabinoid receptor on cells of the immune system and non-Hodgkin's lymphomas. Leuk Lymphoma 2007; 48: 1389–1399.

    CAS  Google Scholar 

  80. Lindgren JA, Stenke L, Mansour M, Edenius C, Lauren L, Nasman-Glaser B et al. Formation and effects of leukotrienes and lipoxins in human bone marrow. J Lipid Mediat 1993; 6: 313–320.

    CAS  Google Scholar 

  81. Bautz F, Denzlinger C, Kanz L, Mohle R . Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood 2001; 97: 3433–3440.

    CAS  Google Scholar 

  82. Vore SJ, Eling TE, Danilowicz M, Tucker AN, Luster MI . Regulation of murine hematopoiesis by arachidonic acid metabolites. Int J Immunopharmacol 1989; 11: 435–442.

    CAS  Google Scholar 

  83. Braccioni F, Dorman SC, O’byrne PM, Inman MD, Denburg JA, Parameswaran K et al. The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects. J Allergy Clin Immunol 2002; 110: 96–101.

    CAS  Google Scholar 

  84. Elsas PX, Queto T, Mendonca-Sales SC, Elsas MI, Kanaoka Y, Lam BK . Cysteinyl leukotrienes mediate the enhancing effects of indomethacin and aspirin on eosinophil production in murine bone marrow cultures. Br J Pharmacol 2008; 153: 528–535.

    CAS  Google Scholar 

  85. Kozubik A, Hofmanova J, Pospisil M, Netikova J, Hola J, Lojek A . Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse. Int J Radiat Biol 1994; 65: 369–377.

    CAS  Google Scholar 

  86. Lu L, Pelus LM, Piacibello W, Moore MA, Hu W, Broxmeyer HE . Prostaglandin E acts at two levels to enhance colony formation in vitro by erythroid (BFU-E) progenitor cells. Exp Hematol 1987; 15: 765–771.

    CAS  Google Scholar 

  87. Rossi GB, Migliaccio AR, Migliaccio G, Lettieri F, Di RM, Peschle C et al. In vitro interactions of PGE and cAMP with murine and human erythroid precursors. Blood 1980; 56: 74–79.

    CAS  Google Scholar 

  88. Estrov Z, Halperin DS, Coceani F, Freedman MH . Modulation of human marrow haematopoiesis by leucotrienes in vitro. Br J Haematol 1988; 69: 321–327.

    CAS  Google Scholar 

  89. Chung JW, Kim GY, Mun YC, Ahn JY, Seong CM, Kim JH . Leukotriene B4 pathway regulates the fate of the hematopoietic stem cells. Exp Mol Med 2005; 37: 45–50.

    CAS  Google Scholar 

  90. Pelus LM . Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony-forming units-granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha. J Immunol 1989; 143: 4171–4179.

    CAS  Google Scholar 

  91. Bertolini A, Ottani A, Sandrini M . Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks. Curr Med Chem 2002; 9: 1033–1043.

    CAS  Google Scholar 

  92. Lapidot T, Dar A, Kollet O . How do stem cells find their way home? Blood 2005; 106: 1901–1910.

    CAS  Google Scholar 

  93. Levesque JP, Leavesley DI, Niutta S, Vadas M, Simmons PJ . Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins. J Exp Med 1995; 181: 1805–1815.

    CAS  Google Scholar 

  94. Papayannopoulou T, Priestley GV, Nakamoto B, Zafiropoulos V, Scott LM . Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over beta(2)-integrins and selectins. Blood 2001; 98: 2403–2411.

    CAS  Google Scholar 

  95. Peled A, Kollet O, Ponomaryov T, Petit I, Franitza S, Grabovsky V et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000; 95: 3289–3296.

    CAS  Google Scholar 

  96. Vermeulen M, Le PF, Gagnerault MC, Mary JY, Sainteny F, Lepault F . Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells. Blood 1998; 92: 894–900.

    CAS  Google Scholar 

  97. van der Loo JC, Xiao X, McMillin D, Hashino K, Kato I, Williams DA . VLA-5 is expressed by mouse and human long-term repopulating hematopoietic cells and mediates adhesion to extracellular matrix protein fibronectin. J Clin Invest 1998; 102: 1051–1061.

    CAS  Google Scholar 

  98. Katayama Y, Hidalgo A, Peired A, Frenette PS . Integrin alpha4beta7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation. Blood 2004; 104: 2020–2026.

    CAS  Google Scholar 

  99. Qian H, Georges-Labouesse E, Nystrom A, Domogatskaya A, Tryggvason K, Jacobsen SE et al. Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells. Blood 2007; 110: 2399–2407.

    CAS  Google Scholar 

  100. Qian H, Tryggvason K, Jacobsen SE, Ekblom M . Contribution of alpha6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with alpha4 integrins. Blood 2006; 107: 3503–3510.

    CAS  Google Scholar 

  101. Schmits R, Filmus J, Gerwin N, Senaldi G, Kiefer F, Kundig T et al. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity. Blood 1997; 90: 2217–2233.

    CAS  Google Scholar 

  102. Sackstein R . The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing. J Invest Dermatol 2004; 122: 1061–1069.

    CAS  Google Scholar 

  103. Katayama Y, Hidalgo A, Furie BC, Vestweber D, Furie B, Frenette PS . PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and alpha4 integrin. Blood 2003; 102: 2060–2067.

    CAS  Google Scholar 

  104. Frenette PS, Subbarao S, Mazo IB, von Andrian UH, Wagner DD . Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc Natl Acad Sci USA 1998; 95: 14423–14428.

    CAS  Google Scholar 

  105. Kollet O, Spiegel A, Peled A, Petit I, Byk T, Hershkoviz R et al. Rapid and efficient homing of human CD34(+)CD38(-/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 2001; 97: 3283–3291.

    CAS  Google Scholar 

  106. Matsuzaki Y, Kinjo K, Mulligan RC, Okano H . Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity 2004; 20: 87–93.

    CAS  Google Scholar 

  107. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283: 845–848.

    CAS  Google Scholar 

  108. Brenner S, Whiting-Theobald N, Kawai T, Linton GF, Rudikoff AG, Choi U et al. CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells. Stem Cells 2004; 22: 1128–1133.

    CAS  Google Scholar 

  109. Kahn J, Byk T, Jansson-Sjostrand L, Petit I, Shivtiel S, Nagler A et al. Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation. Blood 2004; 103: 2942–2949.

    CAS  Google Scholar 

  110. Goichberg P, Kalinkovich A, Borodovsky N, Tesio M, Petit I, Nagler A et al. cAMP-induced PKCzeta activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors. Blood 2006; 107: 870–879.

    CAS  Google Scholar 

  111. Ghosh S, Preet A, Groopman JE, Ganju RK . Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes. Mol Immunol 2006; 43: 2169–2179.

    CAS  Google Scholar 

  112. Coopman K, Smith LD, Wright KL, Ward SG . Temporal variation in CB2R levels following T lymphocyte activation: evidence that cannabinoids modulate CXCL12-induced chemotaxis. Int Immunopharmacol 2007; 7: 360–371.

    CAS  Google Scholar 

  113. Jorda MA, Verbakel SE, Valk PJ, Vankan-Berkhoudt YV, Maccarrone M, Finazzi-Agro A et al. Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood 2002; 99: 2786–2793.

    CAS  Google Scholar 

  114. Maestroni GJ . The endogenous cannabinoid 2-arachidonoyl glycerol as in vivo chemoattractant for dendritic cells and adjuvant for Th1 response to a soluble protein. FASEB J 2004; 18: 1914–1916.

    CAS  Google Scholar 

  115. Mestre L, Correa F, Docagne F, Clemente D, Guaza C . The synthetic cannabinoid WIN 55,212-2 increases COX-2 expression and PGE2 release in murine brain-derived endothelial cells following Theiler's virus infection. Biochem Pharmacol 2006; 72: 869–880.

    CAS  Google Scholar 

  116. Rajesh M, Mukhopadhyay P, Batkai S, Hasko G, Liaudet L, Huffman JW et al. CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion. Am J Physiol Heart Circ Physiol 2007; 293: H2210–H2218.

    CAS  Google Scholar 

  117. Palazuelos J, Davoust N, Julien B, Hatterer E, Aguado T, Mechoulam R et al. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J Biol Chem 2008; 283: 13320–13329.

    CAS  Google Scholar 

  118. Rosch S, Ramer R, Brune K, Hinz B . R(+)-methanandamide and other cannabinoids induce the expression of cyclooxygenase-2 and matrix metalloproteinases in human nonpigmented ciliary epithelial cells. J Pharmacol Exp Ther 2006; 316: 1219–1228.

    Google Scholar 

  119. Alberich JM, Rayman N, Tas M, Verbakel SE, Battista N, van LK et al. The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner. Blood 2004; 104: 526–534.

    Google Scholar 

  120. Kurihara R, Tohyama Y, Matsusaka S, Naruse H, Kinoshita E, Tsujioka T et al. Effects of peripheral cannabinoid receptor ligands on motility and polarization in neutrophil-like HL60 cells and human neutrophils. J Biol Chem 2006; 281: 12908–12918.

    CAS  Google Scholar 

  121. McQuibban GA, Butler GS, Gong JH, Bendall L, Power C, Clark-Lewis I et al. Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 2001; 276: 43503–43508.

    CAS  Google Scholar 

  122. Thomas BF, Gilliam AF, Burch DF, Roche MJ, Seltzman HH . Comparative receptor binding analyses of cannabinoid agonists and antagonists. J Pharmacol Exp Ther 1998; 285: 285–292.

    CAS  Google Scholar 

  123. Pertwee RG . Pharmacology of cannabinoid receptor ligands. Curr Med Chem 1999; 6: 635–664.

    CAS  Google Scholar 

  124. Murineddu G, Lazzari P, Ruiu S, Sanna A, Loriga G, Manca I et al. Tricyclic pyrazoles. 4. Synthesis and biological evaluation of analogues of the robust and selective CB2 cannabinoid ligand 1-(2′,4′-dichlorophenyl)-6-methyl-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c ]pyrazole-3-carboxamide. J Med Chem 2006; 49: 7502–7512.

    CAS  Google Scholar 

  125. Pereira JP, An J, Xu Y, Huang Y, Cyster JG . Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat Immunol 2009; 10: 403–411.

    CAS  Google Scholar 

  126. Del PA, Shao WH, Mitola S, Santoro G, Sozzani S, Haribabu B . Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function. Blood 2007; 109: 626–631.

    Google Scholar 

  127. Shin EH, Lee HY, Bae YS . Leukotriene B4 stimulates human monocyte-derived dendritic cell chemotaxis. Biochem Biophys Res Commun 2006; 348: 606–611.

    CAS  Google Scholar 

  128. Moreno JJ . Differential effects of arachidonic and eicosapentaenoic acid-derived eicosanoids on polymorphonuclear transmigration across endothelial cell cultures. J Pharmacol Exp Ther 2009; 331: 1111–1117.

    CAS  Google Scholar 

  129. Belanger C, Elimam H, Lefebvre J, Borgeat P, Marleau S . Involvement of endogenous leukotriene B4 and platelet-activating factor in polymorphonuclear leucocyte recruitment to dermal inflammatory sites in rats. Immunology 2008; 124: 295–303.

    CAS  Google Scholar 

  130. Bautz F, Denzlinger C, Kanz L, Mohle R . Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood 2001; 97: 3433–3440.

    CAS  Google Scholar 

  131. Boehmler AM, Drost A, Jaggy L, Seitz G, Wiesner T, Denzlinger C et al. The CysLT1 ligand leukotriene D4 supports alpha4beta1- and alpha5beta1-mediated adhesion and proliferation of CD34+ hematopoietic progenitor cells. J Immunol 2009; 182: 6789–6798.

    CAS  Google Scholar 

  132. Fowler CJ . Possible involvement of the endocannabinoid system in the actions of three clinically used drugs. Trends Pharmacol Sci 2004; 25: 59–61.

    CAS  Google Scholar 

  133. Nirodi CS, Crews BC, Kozak KR, Morrow JD, Marnett LJ . The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells. Proc Natl Acad Sci USA 2004; 101: 1840–1845.

    CAS  Google Scholar 

  134. Sang N, Zhang J, Chen C . COX-2 oxidative metabolite of endocannabinoid 2-AG enhances excitatory glutamatergic synaptic transmission and induces neurotoxicity. J Neurochem 2007; 102: 1966–1977.

    CAS  Google Scholar 

  135. Huang SK, Peters-Golden M . Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time? Chest 2008; 133: 1442–1450.

    CAS  Google Scholar 

  136. Guerrero AT, Verri Jr WA, Cunha TM, Silva TA, Schivo IR, Dal-Secco D et al. Involvement of LTB4 in zymosan-induced joint nociception in mice: participation of neutrophils and PGE2. J Leukoc Biol 2008; 83: 122–130.

    CAS  Google Scholar 

  137. Nilsson O, Fowler CJ, Jacobsson SO . The cannabinoid agonist WIN 55,212-2 inhibits TNF-alpha-induced neutrophil transmigration across ECV304 cells. Eur J Pharmacol 2006; 547: 165–173.

    CAS  Google Scholar 

  138. Goichberg P, Kalinkovich A, Borodovsky N, Tesio M, Petit I, Nagler A et al. cAMP-induced PKCzeta activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors. Blood 2006; 107: 870–879.

    CAS  Google Scholar 

  139. Salcedo R, Zhang X, Young HA, Michael N, Wasserman K, Ma WH et al. Angiogenic effects of prostaglandin E2 are mediated by up-regulation of CXCR4 on human microvascular endothelial cells. Blood 2003; 102: 1966–1977.

    CAS  Google Scholar 

  140. Klein TW, Newton C, Larsen K, Lu L, Perkins I, Nong L et al. The cannabinoid system and immune modulation. J Leukoc Biol 2003; 74: 486–496.

    CAS  Google Scholar 

  141. Pertwee RG . Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 2006; 147 (Suppl 1): S163–S171.

    CAS  Google Scholar 

  142. Izumi T, Yokomizo T, Obinata H, Ogasawara H, Shimizu T . Leukotriene receptors: classification, gene expression, and signal transduction. J Biochem 2002; 132: 1–6.

    CAS  Google Scholar 

  143. Sugimoto Y, Narumiya S . Prostaglandin E receptors. J Biol Chem 2007; 282: 11613–11617.

    CAS  Google Scholar 

  144. Desouza IA, Franco-Penteado CF, Camargo EA, Lima CS, Teixeira SA, Muscara MN et al. Inflammatory mechanisms underlying the rat pulmonary neutrophil influx induced by airway exposure to staphylococcal enterotoxin type A. Br J Pharmacol 2005; 146: 781–791.

    CAS  Google Scholar 

  145. Lemos HP, Grespan R, Vieira SM, Cunha TM, Verri Jr WA, Fernandes KS et al. Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production. Proc Natl Acad Sci USA 2009; 106: 5954–5959.

    CAS  Google Scholar 

  146. Burstein SH, Zurier RB . Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J 2009; 11: 109–119.

    CAS  Google Scholar 

  147. Fourie AM . Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase. Curr Opin Investig Drugs 2009; 10: 1173–1182.

    CAS  Google Scholar 

  148. Lazarus M . The differential role of prostaglandin E2 receptors EP3 and EP4 in regulation of fever. Mol Nutr Food Res 2006; 50: 451–455.

    CAS  Google Scholar 

  149. Narumiya S . Prostanoids in immunity: roles revealed by mice deficient in their receptors. Life Sci 2003; 74: 391–395.

    CAS  Google Scholar 

  150. Scher JU, Pillinger MH . The anti-inflammatory effects of prostaglandins. J Investig Med 2009; 57: 703–708.

    CAS  Google Scholar 

  151. Stenke L, Mansour M, Edenius C, Reizenstein P, Lindgren JA . Formation and proliferative effects of lipoxins in human bone marrow. Biochem Biophys Res Commun 1991; 180: 255–261.

    CAS  Google Scholar 

  152. Stenke L, Mansour M, Reizenstein P, Lindgren JA . Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor. Blood 1993; 81: 352–356.

    CAS  Google Scholar 

  153. Claesson HE, Dahlberg N, Gahrton G . Stimulation of human myelopoiesis by leukotriene B4. Biochem Biophys Res Commun 1985; 131: 579–585.

    CAS  Google Scholar 

  154. Lu L, Pelus LM, Broxmeyer HE . Modulation of the expression of HLA-DR (Ia) antigens and the proliferation of human erythroid (BFU-E) and multipotential (CFU-GEMM) progenitor cells by prostaglandin E. Exp Hematol 1984; 12: 741–748.

    CAS  Google Scholar 

  155. Lu L, Pelus LM, Broxmeyer HE, Moore MA, Wachter M, Walker D et al. Enhancement of the proliferation of human marrow erythroid (BFU-E) progenitor cells by prostaglandin E requires the participation of OKT8-positive T lymphocytes and is associated with the density expression of major histocompatibility complex class II antigens on BFU-E. Blood 1986; 68: 126–133.

    CAS  Google Scholar 

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Acknowledgements

Supported by NIH Grants HL069669, HL079654 and HL096305 (to LMP). JH is supported by training Grant DK07519. Flow cytometry was performed in the Flow Cytometry Resource Facility of the Indiana University Simon Cancer Center (NCI P30 CA082709).

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    J Hoggatt & L M Pelus

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Hoggatt, J., Pelus, L. Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking. Leukemia 24, 1993–2002 (2010). https://doi.org/10.1038/leu.2010.216

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