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

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-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.

• Authors: Shuxia Yang, Carlos Milla, Angela Panoskaltsis-Mortari, Samuel Hawgood, Bruce R Blazar, Imad Y Haddad
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 27 Issue 3 Pg. 297-305 (Sep 2002) ISSN: 1044-1549 [Print] United States
• PMID: 12204891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proteolipids
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Proteins
• Pulmonary Surfactants
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Interferon-gamma

Topics

• Animals
• Bone Marrow Transplantation (physiology)
• Bronchoalveolar Lavage Fluid
• Humans
• Interferon-gamma (metabolism)
• Lung (metabolism, pathology)
• Macrophages, Alveolar (metabolism)
• Mice
• Mice, Mutant Strains
• Nitric Oxide (metabolism)
• Pneumonia (prevention & control)
• Proteolipids (genetics, metabolism, pharmacology)
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Proteins
• Pulmonary Surfactants (genetics, metabolism, pharmacology)
• Survival Rate
• T-Lymphocytes (drug effects, physiology)
• Transplantation, Homologous
• Tumor Necrosis Factor-alpha (metabolism)