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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 5, May, 2001 527-536

Human Surfactant Protein A Suppresses T Cell-Dependent Inflammation and Attenuates the Manifestations of Idiopathic Pneumonia Syndrome in Mice

Shuxia Yang, Carlos Milla, Angela Panoskaltsis-Mortari, David H. Ingbar, Bruce R. Blazar, and Imad Y. Haddad

Department of Pediatrics, Division of Pulmonary and Critical Care; Division of Bone Marrow Transplantation; Cancer Center; and Department of Medicine, University of Minnesota, Minneapolis, Minnesota

We have previously shown an association between growth factor-induced upregulation of surfactant protein (SP)-A and suppression of alveolar inflammation in our murine model of donor T cell-dependent lung dysfunction after bone-marrow transplantation, referred to as idiopathic pneumonia syndrome (IPS). We hypothesized that SP-A protects the lung in vivo from IPS injury by downregulation of alveolar inflammation. Human SP-A (100 µg), purified by n-butanol extraction or preparative isoelectric focusing, was transtracheally instilled on Day 4 after BMT during a time of in vivo donor T-cell activation. At 48 h after treatment, immunohistochemical staining of lung sections showed that SP-A did not alter T cell- dependent cellular infiltration. However, macrophages from SP-A-instilled mice were less injured and spontaneously produced less tumor necrosis factor-alpha than did cells from buffer-instilled mice. Although exogenous SP-A did not significantly alter bronchoalveolar lavage fluid (BALF) high levels of total protein (TP), an inverse correlation between BALF SP-A and TP concentrations (r = -0.65; P = 0.02) was observed in SP-A-treated but not in buffer-instilled mice. The only difference between the effects of the two sources of SP-A was that butanol-extracted SP-A, but not isoelectric focusing-purified SP-A, suppressed the interferon-gamma /nitric oxide pathway. We conclude that SP-A downregulates T cell-dependent alveolar inflammation by multiple pathways leading to decreased IPS injury.

Abbreviations: bronchoalveolar lavage fluid, BALF; bone marrow, BM; marrow cells supplemented with spleen cells, BMS; BM transplanation, BMT; cyclophosphamide, Cy; enzyme-linked immunosorbent assay, ELISA; interferon, IFN; immunoglobulin, Ig; idiopathic pneumonia syndrome, IPS; keratinocyte growth factor, KGF; lactic dehydrogenase, LDH; lipopolysaccharide, LPS; nitric oxide, NO; phosphate-buffered saline, PBS; sodium dodecyl sulfate, SDS; standard error, SE; surfactant protein, SP; total body irradiation, TBI; tumor necrosis factor, TNF; total protein, TP.




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