Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo

The role of surfactant-associated protein (SP) A in the mediation of pulmon ary responses to bacterial lipopolysaccharide (LPS) was assessed in vivo wi th SP-A gene-targeted [SP-deficient; SP-A(-/-)] and wild-type [SP-A(+/+)] m ice. Concentrations of tumor necrosis factor (TNF);or, macrophage inflammat ory protein-2, and nitric oxide were determined in recovered bronchoalveola r lavage fluid after intratracheal administration of LPS. SP-A(-/-) mice pr oduced significantly more TNF-alpha and nitric oxide than SP-A(+/+) mice af ter LPS treatment. Intratracheal administration of human SP-A (1 mg/kg) to SP-A(-/-) mice restored regulation of TNF-alpha, macrophage inflammatory pr otein-2, and nitric oxide production to that of SP-A(+/+) mice, Other marke rs of lung injury including bronchoalveolar fluid protein, phospholipid con tent, and neutrophil numbers were not influenced by SP-A. Data from experim ents designed to test possible mechanisms of SP-A-mediated suppression sugg est that neither binding of LPS by SP-A nor enhanced LPS clearance are the primary means of inhibition. Our data and others suggest that SP-A acts dir ectly on immune cells to suppress LPS-induced inflammation. These results d emonstrate that endogenous or exogenous SP-A inhibits pulmonary LPS-induced cytokine and nitric oxide production in vivo.