Pulmonary surfactant lipids inhibit prostanoid production of guinea pig alveolar macrophages.
Changes in the amount and composition of pulmonary surfactant are important features of the adult respiratory distress syndrome. The goal of the present study was to investigate the effects of natural surfactant material and several of its lipid components on prostanoid production and superoxide generation by guinea pig alveolar macrophages. Natural surfactant (10-500 micrograms/ml) inhibited (up to 65%) prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) production elicited by platelet-activating factor (PAF, 10(-6) M) and arachidonic acid (5 x 10(-6) M) but not fMet-Leu-Phe (10(-7) M). Dioleyl-phosphatidylglycerol (diOPG, 1-100 micrograms/ml) and dioleyl-phosphatidylcholine (diOPC, 1-100 micrograms/ml) prevented fMet-Leu-Phe- and PAF-stimulated prostanoid release in a concentration-dependent fashion with a maximal inhibition of 94%. DiOPC (100 microgram/ml) also inhibited arachidonic acid induced PGE2 production by 67%. Phosphatidylcholine (100 micrograms/ml) and sphingomyelin (10-100 micrograms/ml) significantly attenuated TxB2 production elicited by arachidonic acid. Neither PAF- nor fMet-Leu-Phe-stimulated superoxide production was affected significantly by natural surfactant and its lipid components with the exception of phosphatidylcholine. At a concentration of 100 micrograms/ml, phosphatidylcholine decreased superoxide production by about 57% in response to PAF. These results show that diOPC and diOPG are capable of inhibiting prostanoid production of guinea pig alveolar macrophages in response to inflammatory stimuli and suggest that a decrease in the diOPG and diOPC content of surfactant would lead to enhanced intrapulmonary formation of prostanoids and consequently to the deterioration of pulmonary function in the adult respiratory distress syndrome.
Földes-Filep
E
E
Research Center, Maisonneuve-Rosemont Hospital, University of Montréal, Canada.
Sirois
P
P
Filep
J G
JG
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006168:Guinea Pigs; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis*
D011663:Pulmonary Surfactants; D013481:Superoxides; D013929:Thromboxane B2; D015232:Dinoprostone