© 2002 American Thoracic Society DOI: 10.1165/rcmb.2002-0035OC Surfactant Protein A Decreases Lung Injury and Mortality after Murine Marrow TransplantationDepartment of Pediatrics, Divisions of Pulmonary and Critical Care, Bone Marrow Transplantation, and University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota; and Department of Pediatrics, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California Address correspondence to: Imad Y. Haddad, M.D., Department of Pediatrics, University of Minnesota, 420 Delaware Street S.E., Minneapolis, MN 55455. E-mail: hadda003{at}tc.umn.edu
Surfactant protein A (SP-A), a collectin associated with surfactant lipids, can have immune modulatory effects. We hypothesized that exogenous and basal endogenous SP-A can function to suppress donor T-cell–dependent inflammation that occurs during the generation of idiopathic pneumonia syndrome after bone marrow transplantation (BMT). Wild-type and SP-A–deficient mice were conditioned with cyclophosphamide and lethal irradiation and then given allogeneic donor bone marrow plus inflammation-inducing spleen T cells. On Day 7 after BMT, bronchoalveolar lavage fluids from SP-A–deficient mice contained increased numbers of inflammatory cells and higher levels of proinflammatory mediators tumor necrosis factor-
Abbreviations: Bronchoalveolar lavage fluid, BALF • bone marrow, BM • bone marrow supplemented with spleen cells, BMS • bone marrow transplant(ation), BMT • cyclophosphamide, Cy • dynamic compliance, Cdyn • graft-versus-host disease, GVHD • interferon, IFN • idiopathic pneumonia syndrome, IPS • lactic dehydrogenase, LDH • nitric oxide, NO • phosphate-buffered saline, PBS • surfactant protein-A, SP-A • T cell-depleted, TCD • tumor necrosis factor, TNF • total body irradiation, TBI This article has been cited by other articles:
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, interferon-
, and nitric oxide than wild-type mice. Exaggerated inflammation in SP-A–deficient mice was associated with decreased dynamic lung compliance and increased donor T-cell–dependent mortality (P = 0.0007, n = 10). Nitrative stress in alveolar macrophages from SP-A-/--conditioned BMT recipients was higher than for SP-A+/+ mice. Similarly, mice treated with transtracheal human SP-A (50 µg), instilled on Day 4 after BMT during a time of in vivo donor T cell activation, exhibited decreased inflammation and improved early survival compared with buffer-instilled mice. We concluded that basal endogenous SP-A and enhanced alveolar SP-A level modulate donor T-cell–dependent immune responses and prolong survival after allogeneic BMT. 
