Calcium antagonists inhibit oxidative burst and nitrite formation in lipopolysaccharide-stimulated rat peritoneal macrophages.
Activated macrophages are important cell effectors in sepsis/endotoxemia. Superoxide (SO) and nitric oxide (NO) are produced by activated macrophages and are responsible for host defense against microorganisms. Using laser scanning confocal microscopy, we investigated the role of intracellular free calcium ([Ca2+]i) on SO and NO production by rat peritoneal macrophages activated by lipopolysaccharide (LPS). Calcium influx from the extracellular space versus release of calcium from intracellular stores was determined using calcium channel blockers (diltiazem [DIL], verapamil [VER], and nicardipine [NIC]) and dantrolene (DAN), respectively. Cells incubated with LPS had a 30-50 nM increase in [Ca2+]i, (p < .05) compared with non-LPS-treated cells. When stimulated with phorbol myristate acetate, both control and LPS-treated cells sustained a comparable increase in [Ca2+]i, but [Ca2+]i, remained elevated 30 min later in LPS-treated cells. Calcium channel blockers and DAN reduced phorbol myristate acetate-stimulated SO and LPS-stimulated NO production at all concentrations tested (p < .05). Although increased extracellular calcium influx and calcium from intracellular stores are important regulators of SO and NO production in macrophages, extracellular calcium influx seems to have the predominant effect. Calcium antagonists may modulate the inflammatory response via their effects on macrophages.
Hotchkiss
R S
RS
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Bowling
W M
WM
Karl
I E
IE
Osborne
D F
DF
Flye
M W
MW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009573:Nitrites / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D008070:Lipopolysaccharides; D009573:Nitrites; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium