Inhibition by pulmonary surfactant Curosurf of secretory phospholipase A2 expression in guinea-pig alveolar macrophages.
Replacement therapy with exogenous surfactant has been proven successful in animal models of acute respiratory distress syndrome (ARDS). Here, we investigated the effect of seminatural surfactant Curosurf on the expression of secretory phospholipase A2 (sPLA2) in guinea-pig alveolar macrophages (AM). The latter produced an sPLA2 activity whose level was markedly reduced when culture medium was supplemented with Curosurf. This effect was concentration-dependent and was accompanied by a decrease in sPLA2 mRNA levels. By contrast, when AM were first cultured for 20 hr and then incubated with Curosurf, no significant change was observed in their sPLA2 activity. Finally, f-Met-Leu-Phe (FMLP)-induced thromboxane B2 release from AM was not altered by Curosurf, indicating that the inhibition of sPLA2 expression cannot be attributed to a nonspecific membraneous effect of Curosurf. These findings show that pulmonary surfactant modulates the expression of sPLA2 in AM and suggest that this effect may account for the clinical efficacy of surfactant replacement therapy in ARDS.
Hidi
R
R
Unité Associée Institut Pasteur-INSERM N 285, Paris, France.
Vial
D
D
Havet
N
N
Berger
A
A
Vargaftig
B B
BB
Touqui
L
L
D000818:Animals; D001688:Biological Products; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010743:Phospholipids; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy
D001688:Biological Products; D004791:Enzyme Inhibitors; D010743:Phospholipids; D011663:Pulmonary Surfactants; D010741:Phospholipases A; D054467:Phospholipases A2; C068291:poractant alfa