Endothelin-stimulated monocyte supernatants enhance neutrophil superoxide production.
Endothelin-1 (ET-1) is a vasoconstrictive peptide released by ischemic/injured endothelium which increases intracellular ionized calcium [Ca2+]i in vascular smooth muscle. Previous work from this lab has shown that ET-1 also increases human peripheral blood monocyte [Ca2+]i, and that 24 h incubation of monocytes with 10(-9) M ET-1 causes production of prostaglandin E2 and interleukin-6. In these studies, ET-1-stimulated monocyte supernatants were evaluated for their effect on neutrophil superoxide production. While ET-1 alone had no direct effect, incubation of neutrophils for 20 min in ET-1-stimulated monocyte supernatants resulted in a 10-fold increase in superoxide production over basal levels, 44% as much superoxide production as induced by peptide N-formyl-methionyl-leucyl-phenylalanine (N = 6, p < .001). Monocyte supernatants were analyzed for interleukin-8 (IL-8 or neutrophil activation protein) content by radioimmunoassay. ET-1-stimulation resulted in production of 54% as much IL-8 as lipopolysaccharide controls (N = 6, p < .001). While a number of monokines can activate neutrophils, IL-8 has been shown to be a potent neutrophil activator as well as a superoxide primer. Therefore, ET-1-treated monocytes probably upregulate neutrophil superoxide production via a mechanism which includes IL-8.
Huribal
M
M
Department of Surgery, Bridgeport Hospital, CT, USA.
Kumar
R
R
Cunningham
M E
ME
Sumpio
B E
BE
McMillen
M A
MA
D003574:Cytochrome c Group / Q000032:analysis / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology*; D004926:Escherichia coli / Q000737:chemistry; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D003574:Cytochrome c Group; D016232:Endothelins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013481:Superoxides