Modified natural porcine surfactant modulates tobacco smoke-induced stressresponse in human monocytes

Tobacco smoke (TS) is a potent source of oxidants and oxidative stress is a n important mechanism by which TS exerts its toxicity in the lung. We have shown that TS induces heat shock (HS)/stress protein (HSP) synthesis in hum an monocytes. Pulmonary surfactant (PS) whose major physiological function is to confer mechanical stability to alveoli, also modulates oxidative meta bolism and other pro-inflammatory functions of monocytes-macrophages. In or der to determine whether PS alters the stress response induced by TS, we in cubated human peripheral blood monocytes overnight with modified natural po rcine surfactant (Curosurf(R)) (1mg/ml) before exposure to TS. Curosurf(R) decreased TS-induced, but not MS-induced, expression of the major cytosolic , inducible 72kD HSP (Hsp70). Furthermore, TS-generated superoxide anions p roduction was significantly decreased by Curosurf(R) in an acellular system , suggesting a direct scavenging effect of PS. We also examined the effects of TS and PS on monocytes ultrastructure. Monocytes incubated with Curosur f(R) presented smoother cell membranes than control monocytes, while TS-ind uced monocyte vacuolization was, at least in part, prevented by Curosurf(R) . Taken together, our data suggest that PS plays a protective role against oxygen radical-mediated, TS-induced cellular stress responses.