SURFACTANT PROTEIN-A PROTECTS GROWING CELLS AND REDUCES TNF-ALPHA ACTIVITY FROM LPS-STIMULATED MACROPHAGES

In addition to its effect on surfactant lipids, surfactant protein (SP )-A promotes host defense. To define further the role of SP-A in regul ating immune cell function, we evaluated the effect of SP-A on lipopol ysaccharide (LPS)-activated alveolar macrophages in two settings. Firs t, cocultured LPS-activated macrophages significantly inhibited lung f ibroblast growth, but SP-A (added daily) attenuated this effect. Both LPS and SP-A acted via macrophages rather than directly on the fibrobl asts, at least partially by affecting tumor necrosis factor (TNF)-alph a activity. TNF-alpha reproduced the growth suppression, anti-TNF-alph a antibodies attenuated the effect of LPS-activated macrophages, and S P-A reduced TNF-alpha activity in conditioned medium. Second, SP-A red uced TNF-alpha activity in medium from isolated LPS-stimulated macroph ages. The effects of SP-A were noted with or without serum, were dose- dependent and reversible, and were seen with two different serotypes o f smooth LPS. Equimolar concentrations of immunoglobulin G and C1q had no effect. Thus SP-A both enhances host defense and modulates immune functions of alveolar macrophages.