Curosurf modulates cAMP accumulation in human monocytes through a membrane-controlled mechanism.
The cellular mechanisms by which pulmonary surfactant exerts its effects, including anti-inflammatory or proinflammatory effects, have remained elusive. To address the issue of whether plasma membrane modifications represent a target for these mechanisms, we designed an experimental protocol involving the determination of changes in cAMP levels under membrane-dependent or -independent stimulatory pathways. The effects of a modified natural porcine surfactant, Curosurf, and the major surfactant protein A were evaluated on resting and stimulated cAMP levels of human monocytes. We found that agents that elevate intracellular cAMP exhibit different susceptibilities toward a preexposure to Curosurf. The rise in cAMP induced by membrane-active agents such as cholera toxin or the diterpene forskolin was significantly inhibited by monocyte preexposure to Curosurf. In contrast, the rise in cAMP induced by the membrane-permeant phosphodiesterase inhibitor 3-isobutyl-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 effects of cholera toxin or forskolin is involved in the inhibition of cAMP accumulation caused by Curosurf.
Pinot
F
F
Laboratoire de Physiologie Respiratoire, Unité de Formation et de Recherche Cochin Port-Royal, Assistance Publique-Hôpitaux de Paris Université Paris V, France.
Walti
H
H
Haagsman
H P
HP
Polla
B S
BS
Bachelet
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D001426:Bacterial Proteins / Q000494:pharmacology; D001688:Biological Products; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004338:Drug Combinations; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010743:Phospholipids; D011498:Protein Precursors / Q000494:pharmacology; D011510:Proteolipids / Q000494:pharmacology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D001426:Bacterial Proteins; D001688:Biological Products; D004338:Drug Combinations; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D011498:Protein Precursors; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; C068291:poractant alfa; D015056:1-Methyl-3-isobutylxanthine