Hexachlorocyclohexanes, potent stimuli of O2- production and calcium release in human polymorphonuclear leukocytes.
alpha-, gamma-, and delta-Hexachlorocyclohexane (HCCH), but not the beta-isomer, are shown to be potent stimuli for the production of superoxide anion (O2-) and the release of calcium in human polymorphonuclear leukocytes (PMNs). Although O2- production occurs in the absence of exogenous divalent cations, calcium (0.5 mmol/L) enhances O2- production by 50%. In addition, gamma-HCCH-induced O2- production is sensitive (IC50-30-40 mumol/L) to inhibition by the putative intracellular antagonist, 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8). Furthermore, it is shown that gamma-HCCH induces a marked loss of membrane-associated calcium as monitored by chlortetracycline fluorescence. This pool of calcium appears to encompass the same pool released by the formylated tripeptide, formylmethionylleucylphenylalanine (FMLP). We suggest that the HCCHs represent a new class of stimuli of O2- production and calcium mobilization in PMNs.
D002118:Calcium / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D010101:Oxygen Consumption; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D001556:Hexachlorocyclohexane; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium