Surfactant protein A decreases lung injury and mortality after murine marrow transplantation.
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-alpha, interferon-gamma, 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 micro g), 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.
Yang
Shuxia
S
Department of Pediatrics, Divisions of Pulmonary and Critical Care, Bone Marrow Transplantation, and University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Milla
Carlos
C
Panoskaltsis-Mortari
Angela
A
Hawgood
Samuel
S
Blazar
Bruce R
BR
Haddad
Imad Y
IY
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism; D011014:Pneumonia / Q000517:prevention & control*; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma