Curosurf modulates cAMP accumulation in human monocytes through a membrane-controlled mechanism

Curosurf modulates cAMP accumulation in human monocytes through a membrane- controlled mechanism. Am. J. Physiol. Lung Cell. Mol. PhysioE. 278: L99-L10 4, 2000.-The cellular mechanisms by which pulmonary surfactant exerts its e ffects, including anti-inflammatory or proinflammatory effects, have remain ed elusive. To address the issue of whether plasma membrane modifications r epresent a target for these mechanisms, we designed an experimental protoco l involving the determination of changes in cAMP levels under membrane-depe ndent or -independent stimulatory pathways. The effects of a modified natur al porcine surfactant, Curosurf, and the major surfactant protein A were ev aluated on resting and stimulated cAMP levels of human monocytes. We found that agents that elevate intracellular cAMP exhibit different susceptibilit ies toward a preexposure to Curosurf. The rise in cAMP induced by membrane- active agents such as cholera toxin or the diterpene forskolin was signific antly inhibited by monocyte preexposure to Curosurf In contrast, the rise i n cAMP induced by the membrane-permeant phosphodiesterase inhibitor 3-isobu tyl-1-methylxanthine or by the Bordetella pertussis toxin adenylate cyclase -hemolysin was unaffected by Curosurf. Surfactant protein A did not affect either cAMP levels or the inhibitory capacity of Curosurf. We suggest that a plasma membrane-associated event affecting the mechanism underlying the e ffects of cholera toxin or forskolin is involved in the inhibition of cAMP accumulation caused by Curosurf.