Endothelin-1 increases intracellular calcium in human monocytes and causes production of interleukin-6.
OBJECTIVE
To define whether endothelin-1, a peptide produced by injured/ischemic endothelium, has any effect on monocyte intracellular calcium and the production of interleukin (IL)-1 and IL-6.


METHODS
Prospective controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimulated for 24 hrs in tissue culture with purified endotoxin or endothelin.


METHODS
Veterans Affairs Medical Center surgical critical care basic science laboratory.


RESULTS
Endothelin-1 increased the intracellular calcium concentration in fura-2 loaded human monocytes to a mean value of 37 +/- 4 nmol. Phytohemagglutinin increased intracellular calcium in control monocytes to a mean value of 97 +/- 12 nmol (n = 15; p < .001). Endothelin had no effect on neutrophil or lymphocyte intracellular calcium. Monocytes incubated with 10(-9) M endothelin significantly increased IL-6 production to values nearly as high as the lipopolysaccharide controls, but did not increase IL-1 production (n = 8; p < .01).


CONCLUSIONS
Endothelin-1 increased intracellular calcium in monocytes and caused production of IL-6.
McMillen
M A
MA
Department of Surgery, Bridgeport Hospital, Yale University, West Haven, CT.
Huribal
M
M
Cunningham
M E
ME
Kumar
R
R
Sumpio
B E
BE
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D004926:Escherichia coli; D016257:Fura-2 / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011446:Prospective Studies; D011863:Radioimmunoassay
D016232:Endothelins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D002118:Calcium; D016257:Fura-2