Surfactant protein A decreases lung injury and mortality after murine marrow transplantation

Shuxia Yang, Carlos Milla, Angela Panoskaltsis-Mortari, Samuel Hawgood, Bruce R. Blazar, Imad Y. Haddad

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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-α, interferon-γ, 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.

Original languageEnglish (US)
Pages (from-to)297-305
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume27
Issue number3
DOIs
StatePublished - Sep 2002

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