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Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease?

Bone Marrow Transplantation volume 34, pages 753–765 (2004)Cite this article

Summary:

Allogeneic hematopoietic stem cell transplantation (SCT) is an important therapeutic option for a number of malignant and nonmalignant conditions but the broader application of this treatment strategy is limited by several side effects. In particular, diffuse lung injury is a major complication of SCT that responds poorly to standard therapeutic approaches and significantly contributes to transplant-related morbidity and mortality. Historically, approximately 50% of all pneumonias seen after SCT have been secondary to infection, but the judicious use of broad-spectrum antimicrobial prophylaxis in recent years has tipped the balance of pulmonary complications from infectious to noninfectious causes. This mini review will discuss the definition, risk factors and pathogeneses of noninfectious lung injury that occurs early after allogeneic SCT.

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References

  1. Clark JG, Madtes DK, Martin TR et al. Idiopathic pneumonia after bone marrow transplantation: cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment. Crit Care Med 1999; 27: 1800–1806.

    CAS  PubMed  Google Scholar 

  2. Crawford S, Hackman R . Clinical course of idiopathic pneumonia after bone marrow transplantation. Am Rev Resp Dis 1993; 147: 1393.

    CAS  PubMed  Google Scholar 

  3. Weiner RS, Mortimer MB, Gale RP et al. Interstitial pneumonitis after bone marrow transplantation. Ann Intern Med 1986; 104: 168–175.

    Article  CAS  PubMed  Google Scholar 

  4. Quabeck K . The lung as a critical organ in marrow transplantation. Bone Marrow Transplant 1994; 14: S19–S28.

    PubMed  Google Scholar 

  5. Crawford S, Longton G, Storb R . Acute graft versus host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia. Bone Marrow Transplant 1993; 12: 225.

    CAS  PubMed  Google Scholar 

  6. Kantrow SP, Hackman RC, Boeckh M et al. Idiopathic pneumonia syndrome: changing spectrum of lung injury after marrow transplantation. Transplantation 1997; 63: 1079–1086.

    CAS  PubMed  Google Scholar 

  7. Afessa B, Litzow MR, Tefferi A . Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 28: 425–434.

    CAS  PubMed  Google Scholar 

  8. Clark J, Hansen J, Hertz M et al. Idiopathic pneumonia syndrome after bone marrow transplantation. Am Rev Resp Dis 1993; 147: 1601–1606.

    CAS  PubMed  Google Scholar 

  9. Wingard JR, Mellits ED, Sostrin MB et al. Interstitial pneumonitis after allogeneic bone marrow transplantation. Nine-year experience at a single institution. Medicine 1988; 67: 175–186.

    CAS  PubMed  Google Scholar 

  10. Yousem SA . The histological spectrum of pulmonary graft-versus-host disease in bone marrow transplant recipients. Hum Pathol 1995; 26: 668–675.

    CAS  PubMed  Google Scholar 

  11. Neiman P, Wasserman PB, Wentworth BB et al. Interstitial pneumonia and cytomegalovirus infection as complications of human marrow transplantation. Transplantation 1973; 15: 478–485.

    CAS  PubMed  Google Scholar 

  12. Yanik G, Hellerstedt B, Custer J et al. Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 395–400.

    CAS  PubMed  Google Scholar 

  13. Robbins RA, Linder J, Stahl MG et al. Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients. Am J Med 1989; 87: 511–518.

    CAS  PubMed  Google Scholar 

  14. Lewis ID, DeFor T, Weisdorf DJ . Increasing incidence of diffuse alveolar hemorrhage following allogeneic bone marrow transplantation: cryptic etiology and uncertain therapy. Bone Marrow Transplant 2000; 26: 539–543.

    CAS  PubMed  Google Scholar 

  15. Metcalf JP, Rennard SI, Reed EC et al. Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group. Am J Med 1994; 96: 327–334.

    Article  CAS  PubMed  Google Scholar 

  16. Sloane J, Depledge M, Powles R et al. Histopathology of the lung after bone marrow transplantation. J Clin Pathol 1983; 36: 546–554.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Wojno KJ, Vogelsang GB, Beschorner WE, Santos GW . Pulmonary hemorrhage as a cause of death in allogeneic bone marrow recipients with severe acute graft-versus-host disease. Transplantation 1994; 57: 88–92.

    CAS  PubMed  Google Scholar 

  18. Capizzi SA, Kumar S, Huneke NE et al. Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27: 1299–1303.

    Article  CAS  PubMed  Google Scholar 

  19. Wilczynski SW, Erasmus JJ, Petros WP et al. Delayed pulmonary toxicity syndrome following high-dose chemotherapy and bone marrow transplantation for breast cancer. Am J Resp Crit Care Med 1998; 157: 565–573.

    CAS  PubMed  Google Scholar 

  20. Bhalla KS, Wilczynski SW, Abushamaa AM et al. Pulmonary toxicity of induction chemotherapy prior to standard or high-dose chemotherapy with autologous hematopoietic support. Am J Resp Crit Care Med 2000; 161: 17–25.

    CAS  PubMed  Google Scholar 

  21. Cahill RA, Spitzer TR, Mazumder A . Marrow engraftment and clincial manifestations of capillary leak syndrome. Bone Marrow Transplantation 1996; 18: 177–184.

    CAS  PubMed  Google Scholar 

  22. Colby C, McAfeem S, Sackstein R et al. Engraftment syndrome following non-myeloablative conditioning therapy and HLA-matched bone marrow transplantation for hematologic malignancy. Blood 2000; 96: 520a.

    Google Scholar 

  23. Nurnberger W, Willers R, Burdach S, Gobel U . Risk factors for capillary leakage syndrome after bone marrow transplantation. Ann Hematol 1997; 74: 221–224.

    CAS  PubMed  Google Scholar 

  24. Weiner RS, Horowitz MM, Gale RP et al. Risk factors for interstitial pneumonitis following bone marrow transplantation for severe aplastic anemia. Br J Haematol 1989; 71: 535.

    CAS  PubMed  Google Scholar 

  25. Meyers JD, Flournoy N, Thomas ED . Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis 1982; 4: 1119–1132.

    CAS  PubMed  Google Scholar 

  26. Atkinson K, Turner J, Biggs JC et al. An acute pulmonary syndrome possibly representing acute graft-versus-host disease involving the lung interstitium. Bone Marrow Transplant 1991; 8: 231.

    CAS  PubMed  Google Scholar 

  27. Della Volpe A, Ferreri AJ, Annaloro C et al. Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total body irradiation. Int J Radiat Oncol Biol Phys 2002; 52: 483–488.

    PubMed  Google Scholar 

  28. Fukuda T, Hackman RC, Guthrie KA et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102: 2777–2785.

    PubMed  Google Scholar 

  29. Down JD, Mauch P, Warhol M et al. The effect of donor T lymphocytes and total-body irradiation on hemopoietic engraftment and pulmonary toxicity following experimental allogeneic bone marrow transplantation. Transplantation 1992; 54: 802–808.

    CAS  PubMed  Google Scholar 

  30. Shankar G, Cohen DA . Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pre-transplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis. Int J Exp Pathol 2001; 82: 101–113.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kelley J . Cytokines of the lung. Am Rev Resp Dis 1990; 141: 765–788.

    CAS  PubMed  Google Scholar 

  32. Piguet P, Collart M, Grau G et al. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature 1990; 344: 245–247.

    CAS  PubMed  Google Scholar 

  33. Schmidt J, Pliver CN, Lepe Zuniga JL et al. Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin-1. A potential role for interleukin-1 in the pathogenesis of silicosis. J Clin Invest 1984; 73: 1462–1472.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Suter P, Suter S, Girardin E et al. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock or sepsis. Am Rev Resp Dis 1992; 145: 1016.

    CAS  PubMed  Google Scholar 

  35. Hyers T, Tricomi S, Dettenmier P, Fowler A . Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Resp Dis 1991; 144: 268.

    CAS  PubMed  Google Scholar 

  36. Bortin M, Ringden O, Horowitz M et al. Temporal relationships between the major complications of bone marrow transplantation for leukemia. Bone Marrow Transplant 1989; 4: 339.

    CAS  PubMed  Google Scholar 

  37. Beschorner W, Saral R, Hutchins G et al. Lymphocytic bronchitis associated with graft versus host disease in recipients of bone marrow transplants. N Engl J Med 1978; 299: 1030–1036.

    CAS  PubMed  Google Scholar 

  38. Piguet PF, Grau GE, Collart MA et al. Pneumopathies of the graft-versus-host reaction. Alveolitis associated with an increased level of tumor necrosis factor MRNA and chronic interstitial pneumonitis. Lab Invest 1989; 61: 37–45.

    CAS  PubMed  Google Scholar 

  39. Clark JG, Madtes DK, Hackman RC et al. Lung injury induced by alloreactive Th1 cells is characterized by host-derived mononuclear cell inflammation and activation of alveolar macrophages. J Immunol 1998; 161: 1913–1920.

    CAS  PubMed  Google Scholar 

  40. Shankar G, Bryson J, Jennings C et al. Idiopathic pneumonia syndrome in mice after allogeneic bone marrow transplantation. Am J Resp Cell Mol Biol 1998; 18: 235–242.

    CAS  Google Scholar 

  41. Cooke KR, Kobzik L, Martin TR et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation. I. The roles of minor H antigens and endotoxin. Blood 1996; 88: 3230–3239.

    CAS  PubMed  Google Scholar 

  42. Cooke KR, Krenger W, Hill GR et al. Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation. Blood 1998; 92: 2571–2580.

    CAS  PubMed  Google Scholar 

  43. Hackman RC, Sale GE . Large airway inflammation as a possi-ble manifestation of a pulmonary graft-versus-host reaction in bone marrow allograft recipients. Lab Invest 1981; 44: 26A.

    Google Scholar 

  44. Connor R, Ramsay N, McGlave P et al. Pulmonary pathology in bone marrow transplant recipients. Lab Invest 1982; 46: 3.

    Google Scholar 

  45. Gerbitz A, Nickoloff BJ, Olkiewicz K et al. A role for TNFa mediated endothelial apoptosis in the development of experimental idiopathic pneumonia syndrome. Tranplantation 2004; in press.

  46. Janin A, Deschaumes C, Daneshpouy M et al. CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications. Blood 2002; 99: 2940–2947.

    CAS  PubMed  Google Scholar 

  47. Salat C, Holler E, Kolb HJ et al. Plasminogen activator inhibitor-1 confirms the diagnosis of hephatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation. Blood 1997; 89: 2184–2188.

    CAS  PubMed  Google Scholar 

  48. Workman D, Clancy JJ . Interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis as a direct result of acute lethal graft-versus-host disease duplicate the histopathology of lung allograft rejection. Transplantation 1994; 58: 207.

    CAS  PubMed  Google Scholar 

  49. Panoskaltsis-Mortari A, Taylor PA, Yaegar TM et al. The critical early proinflammatory events associated with idiopathic pneumonia syndrome in irradiated murine allogenic recipients are due to donor T cell infusion and potentiated by cyclophoshamide. J Clin Invest 1997; 100: 1015–1027.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Cooke K, Kobzik L, Teshima T et al. A role for Fas-Fas ligand but not perforin mediated cytolysis in the development of experimental idiopathic pneumonia syndrome. Blood 2000; 96 (Suppl. 1): 768a.

    Google Scholar 

  51. Gerbitz A, Wilke A, Eissner G et al. Critical role for CD54 (ICAM-1) in the development of experimental indiopathic pneumonia syndrome. Blood 2000; 96 (Suppl. 1): 768a.

    Google Scholar 

  52. Schultz KR, Green GJ, Wensley D et al. Obstructive lung disease in children after allogeneic bone marrow transplantation. Blood 1994; 84: 3212–3220.

    CAS  PubMed  Google Scholar 

  53. Curtis DJ, Smale A, THien F et al. Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 16: 169–173.

    CAS  PubMed  Google Scholar 

  54. Clark JG, Schwartz DA, Flournoy N et al. Risk factors for air-flow obstruction in recipients of bone marrow transplants. Ann Intern Med 1987; 107: 648–656.

    CAS  PubMed  Google Scholar 

  55. Holland HK, Wingard JR, Beschorner WE et al. Bronchiolitis obliterans in bone marrow transplantation and its relationship to chronic graft-versus-host disease and low serum IgG. Blood 1988; 72: 621–627.

    CAS  PubMed  Google Scholar 

  56. Schwarer AP, Hughes JMB, Trotman-Dickenson B et al. A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation. Transplantation 1992; 54: 1002–1008.

    CAS  PubMed  Google Scholar 

  57. Piguet PF, Grau GE, Allet B, Vassalli PJ . Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-versus-host disease. J Exp Med 1987; 166: 1280–1289.

    CAS  PubMed  Google Scholar 

  58. Cooke KR, Hill GR, Gerbitz A et al. Tumor necrosis factor-alpha neutralization reduces lung injury after experimental allogeneic bone marrow transplantation. Transplantation 2000; 70: 272–279.

    CAS  PubMed  Google Scholar 

  59. Hildebrandt GC, Olkiewitz KO, Corrion LA et al. Secretion of TNF-alpha by donor effector cells is critical in the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Blood 2003; 102: 3529.

    Google Scholar 

  60. Hill GR, Crawford JM, Cooke KR et al. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood 1997; 90: 3204–3213.

    CAS  PubMed  Google Scholar 

  61. Cooke K, Hill G, Crawford J et al. Tumor necrosis factor-α production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft versus host disease. J Clin Invest 1998; 102: 1882–1891.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Hattori K, Hirano T, Miyajima H et al. Differential effects of anti-Fas ligand and anti-tumor necrosis factor-α antibodies on acute graft-versus-host disease pathologies. Blood 1998; 91: 4051–4055.

    CAS  PubMed  Google Scholar 

  63. Vallera DA, Taylor PA, Vannice JL et al. Interleukin-1 or tumor necrosis factor-alpha antagonists do not inhibit graft-versus-host disease induced across the major histocompatibility barrier in mice. Transplantation 1995; 60: 1371–1374.

    CAS  PubMed  Google Scholar 

  64. Clark JG, Mandac JB, Dixon AE et al. Neutralization of tumor necrosis factor-alpha action delays but does not prevent lung injury induced by alloreactive T helper 1 cells. Transplantation 2000; 70: 39–43.

    CAS  PubMed  Google Scholar 

  65. Baker MB, Altman NH, Podack ER, Levy RB . The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice. J Exp Med 1996; 183: 2645–2656.

    CAS  PubMed  Google Scholar 

  66. Braun YM, Lowin B, French L et al. Cytotoxic T cells deficient in both functional Fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease. J Exp Med 1996; 183: 657–661.

    CAS  PubMed  Google Scholar 

  67. Haddad I, Ingbar D, Panoskaltsis-Mortari A, Blazar B . Activated alveolar macrophage-derived nitric oxide predicts the development of lung damage after marrow transplantation in mice. Chest 1999; 116 (Suppl. 1): 37S.

    CAS  PubMed  Google Scholar 

  68. Haddad I, Panoskaltsis-Mortari A, Ingbar D et al. High levels of peroxynitrite are generated in the lungs of irradiated mice given cyclophosphamide and allogeneic T cells: a potential mechanism of injury after marrow transplantation. Am J Resp Cell Mol Biol 1999; 20: 1125.

    CAS  Google Scholar 

  69. Smith S, Skerrett S, Chi E et al. The locus of tumor necrosis factor-α action in lung inflammation. Am J Resp Cell Mol Biol 1998; 19: 881.

    CAS  Google Scholar 

  70. Nelson S, Bagby G, Gainton B et al. Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. J Infect Dis 1989; 159: 189.

    CAS  PubMed  Google Scholar 

  71. Ulich TR, Watson LR, Yin SM et al. The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. Am J Pathol 1991; 138: 1485–1496.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Nestel FP, Price KS, Seemayer TA, Lapp WS . Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease. J Exp Med 1992; 175: 405–413.

    CAS  PubMed  Google Scholar 

  73. Hill G, Ferrara J . The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood 2000; 95: 2754–2759.

    CAS  PubMed  Google Scholar 

  74. Cooke K, Gerbitz A, Hill G et al. LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation. J Clin Invest 2001; 107: 1581–1589.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Fegan C, Poynton CH, Whittaker JA . The gut mucosal barrier in bone marrow transplantation. Bone Marrow Transplant 1990; 5: 373–377.

    CAS  PubMed  Google Scholar 

  76. Jackson SK, Parton J, Barnes RA et al. Effect of IgM-enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti-endotoxin antibodies in bone marrow transplantation. Eur J Clin Invest 1993; 23: 540–545.

    CAS  PubMed  Google Scholar 

  77. Holler E, Kolb HJ, Moller A et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 1990; 75: 1011–1016.

    CAS  PubMed  Google Scholar 

  78. Martin T, Rubenfeld G, Ruzinski J . Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. Am J Resp Crit Care Med 1997; 155: 937–944.

    CAS  PubMed  Google Scholar 

  79. Shlomchik WD, Couzens MS, Tang CB et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999; 285: 412–415.

    CAS  PubMed  Google Scholar 

  80. Madtes DK, Crawford SW . Lung injuries associated with graft-versus-host reactions. In: Ferrara JLM, Deeg HJ, Burakoff SJ (eds.). Graft-vs-Host Disease, 2nd edn. Marcel Dekker, Inc.: New York, NY, 1997; 425.

    Google Scholar 

  81. Watanabe T, Kawamura T, Kawamura H et al. Intermediate TCR cells in mouse lung. Their effector function to induce pneumonitis in mice with autoimmune-like graft-versus-host disease. J Immunol 1997; 158: 5805.

    CAS  PubMed  Google Scholar 

  82. Chen W, Chatta K, Rubin W et al. Polymorphic segments of CD45 can serve as targets for GVHD and GVL responses. Blood 1995; 86 (Suppl.) 158a.

    Google Scholar 

  83. Chen W, Chatta GS, Rubin WD et al. T cells for a polymorphic segment of CD45 induce graft-versus-host disease with predominant pulmonary vasculitis. J Immunol 1998; 161: 909–918.

    CAS  PubMed  Google Scholar 

  84. Leblond V, Zouabi H, Sutton L et al. Late CD8+ lymphocytic alveolitis after allogeneic bone marrow transplantation and chronic graft-versus-host disease. Am J Crit Care Med 1994; 150: 1056.

    CAS  Google Scholar 

  85. Milburn HJ, Poulter LW, Prentice HG, Du Bois RM . Pulmonary cell populations in recipients of bone marrow transplants with interstitial pneumonitis. Thorax 1989; 44: 570.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Stein R, Hummel D, Bohn D et al. Lymphocytic pneumonitis following bone marrow transplantation in severe combined immunodeficiency. Am Rev Resp Dis 1991; 143: 1406–1408.

    CAS  PubMed  Google Scholar 

  87. Massard G, Tongiio MW, Wihlm JM, Morand G . The dendritic cell lineage: an ubiquitous antigen-presenting organization. Ann Thorac Surg 1996; 61: 252.

    CAS  PubMed  Google Scholar 

  88. Armstrong LR, Christensen PJ, Paine R et al. Regulation of the immunostimulatory activity of rat pulmonary interstitial dendritic cells by cell–cell interactions and cytokines. Am J Resp Cell Mol Biol 1994; 11: 682.

    CAS  Google Scholar 

  89. Dupuis M, McDonald DM . Dendritic-cell regulation of lung immunity. Am J Resp Cell Mol Biol 1997; 17: 284.

    CAS  Google Scholar 

  90. Christensen PJ, Armstrong LR, Fak JJ et al. Regulation of rat pulmonary dendritic cell immunostimulatory activity by alveolar epithelial cell-derived granulocyte macrophage colony-stimulating factor. Am J Resp Cell Mol Biol 1995; 13: 426.

    CAS  Google Scholar 

  91. van Haarst JM, de Wit HJ, Drexhage HA, Hoogsteden HC . Distribution and immunophenotype of mononuclear and dendritic cells in the human lung. Am J Resp Cell Mol Biol 1994; 10: 487.

    CAS  Google Scholar 

  92. Yousem SA, Ray L, Paradis IL et al. Potential role of dendritic cells in bronchiolitis obliterans in heart-lung transplantation. Ann Thorac Surg 1990; 49: 424.

    CAS  PubMed  Google Scholar 

  93. Teshima T, Ordemann R, Reddy P et al. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat Med 2002; 8: 575–581.

    CAS  PubMed  Google Scholar 

  94. Holt PG, Haining S, Nelson DJ, Sedgwick JD . Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J Immunol 1994; 153: 256–261.

    CAS  PubMed  Google Scholar 

  95. Glode LM, Rosenstreich DL . Genetic control of B cell activation by bacterial lipopolysaccaride is mediated by multiple distinct genes or alleles. J Immunol 1976; 117: 2061–2066.

    CAS  PubMed  Google Scholar 

  96. Poltorak A, Ziaolong H, Smirnova I et al. Defective LPS signaling in C3H/HeJ and C57BL/20ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085–2088.

    CAS  PubMed  Google Scholar 

  97. Watson J, Kelly K, Largen M, Taylor BA . The genetic mapping of a defective LPS response gene in C3H/Hej mice. J Immunol 1978; 120: 422–424.

    CAS  PubMed  Google Scholar 

  98. Sultzer BM, Castagna R, Bandeakar J, Wong P . Lipopolysaccharide nonresponder cells: the C3H/HeJ defect. Immunobiology 1993; 187: 257–271.

    CAS  PubMed  Google Scholar 

  99. Cooke K, Olkiewicz K, Clouthier S et al. Critical role for CD14 and the innate immune response in the induction of experimental acute graft-versus-host disease. Blood 2001; 98 (Suppl. 1): 776a.

    Google Scholar 

  100. Maus U, Herold S, Muth H et al. Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14. Am J Physiol Lung Cell Mol Physiol 2001; 280: L58–L68.

    CAS  PubMed  Google Scholar 

  101. Gomez-Reino JJ, Carmona L, Valverde VR et al. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 2003; 48: 2122–2127.

    CAS  PubMed  Google Scholar 

  102. Martin T, Goodman R . The role of chemokines in the pathophysiology of the acute respiratory distress syndrome (ARDS). In: Hebert C (ed.). Chemokines in Disease. Humana Press: Towata, 1999, 81–110.

    Google Scholar 

  103. DiGiovine B, Lynch J, Martinez F et al. Bronchoalveolar lavage neutrophilia is associated with obliterative bronchiolitis after lung transplantation: role of IL-8. J Immunol 1996; 157: 4194–5202.

    CAS  PubMed  Google Scholar 

  104. Riise GC, Andersson BA, Kjellstrom C et al. Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant. Eur Resp J 1999; 14: 1123–1130.

    CAS  Google Scholar 

  105. Zheng L, Walters EH, Ward C et al. Airway neutrophilia in stable and bronchiolitis obliterans syndrome patients following lung transplantation. Thorax 2000; 55: 53–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Reynaud-Gaubert M, Thomas P, Badier M et al. Early detection of airway involvement in obliterative bronchiolitis after lung transplantation. Functional and bronchoalveolar lavage cell findings. Am J Resp Crit Care Med 2000; 161: 1924–1929.

    CAS  PubMed  Google Scholar 

  107. Elssner A, Vogelmeier C . The role of neutrophils in the pathogenesis of obliterative bronchiolitis after lung transplantation. Transpl Infect Dis 2001; 3: 168–176.

    CAS  PubMed  Google Scholar 

  108. Mackay CR . Chemokines: immunology's high impact factors. Nat Immunol 2001; 2: 95–101.

    CAS  PubMed  Google Scholar 

  109. Kishimoto TK, Walcheck B, Rothlein R . Leukocyte adhesion, trafficking, and migration. In: Ferrara JLM, Deeg HJ, Burakoff SJ (eds.). Graft-vs-Host Disease. Marcel Dekker, Inc.: New York, 1997, 151–178.

    Google Scholar 

  110. Luster AD . Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436–445.

    CAS  PubMed  Google Scholar 

  111. Gerard C, Rollins BJ . Chemokines and disease. Nat Immunol 2001; 2: 108–115.

    CAS  PubMed  Google Scholar 

  112. Luster AD . The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol 2002; 14: 129–135.

    CAS  PubMed  Google Scholar 

  113. Serody JS, Burkett SE, Panoskaltsis-Mortari A et al. T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease. Blood 2000; 96: 2973–2980.

    CAS  PubMed  Google Scholar 

  114. Panoskaltsis-Mortari A, Hermanson JR, Taras E et al. Acceleration of idiopathic pneumonia syndrome (IPS) in the absence of donor MIP-1 alpha (CCL3) after allogeneic BMT in mice. Blood 2003; 101: 3714–3721.

    CAS  PubMed  Google Scholar 

  115. DiCarlo JV, Alexander SR, Agarwal R, Schiffman JD . Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy. J Pediatr Hematol Oncol 2003; 25: 801–805.

    PubMed  Google Scholar 

  116. Haimovitz-Friedman A, Cordon-Cardo C, Bayoumy S et al. Lipopolysaccharide induces disseminated endothelial apoptosis requiring ceramide generation. J Exp Med 1997; 186: 1831–1841.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Paris F, Fuks Z, Kang A et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293: 293–297.

    CAS  PubMed  Google Scholar 

  118. Krijanovski OI, Hill GR, Cooke KR et al. Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease. Blood 1999; 94: 825–831.

    CAS  PubMed  Google Scholar 

  119. Clouthier SG, Cooke KR, Teshima T et al. Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect. Biol Blood Marrow Transplant 2003; 9: 592–603.

    CAS  PubMed  Google Scholar 

  120. Panoskaltsis-Mortari A, Ingbar DH, Jung P et al. KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT. Am J Physiol Lung Cell Mol Physiol 2000; 278: L988–L999.

    CAS  PubMed  Google Scholar 

  121. Pecego R, Hill R, Appelbaum FR et al. Interstitial pneumonitis following autologous bone marrow transplantation. Transplantation 1986; 42: 515–517.

    CAS  PubMed  Google Scholar 

  122. Granena A, Carreras E, Rozman C et al. Interstitial pneumonitis after BMT: 15 years experience in a single institution. Bone Marrow Transplant 1993; 11: 453–458.

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. K R Cooke: Dr Cooke is a National Marrow Donor Program Amy Strelzer-Manasevit Scholar and a fellow of the Robert Wood Johnson Minority Faculty Development Program.

  2. K R Cooke and G Yanik: Drs Cooke and Yanik are recipients of a Translational Research Award from the Leukemia and Lymphoma Society.

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan Cancer Center, Ann Arbor, MI, USA

    K R Cooke & G Yanik

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  1. K R Cooke
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  2. G Yanik
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Correspondence to K R Cooke.

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Cooke, K., Yanik, G. Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease?. Bone Marrow Transplant 34, 753–765 (2004). https://doi.org/10.1038/sj.bmt.1704629

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  • DOI: https://doi.org/10.1038/sj.bmt.1704629

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