Calcium overload toxicity and functional impairment in peritoneal leukocytes elicited by glycogen or interleukin-1 beta.
Although calcium plays an important role in the activation of leukocytes for such processes as eicosanoid biosynthesis, secretion of granular constituents and superoxide generation, sustained high levels of intracellular calcium ions may be toxic. We have previously found that high concentrations of calcium ionophores induce a rapid-onset "calcium overload" toxicity in rat peritoneal leukocytes, in which functional responses such as beta-glucuronidase secretion, superoxide generation and leukotriene B4 synthesis are greatly attenuated, and some leakage of cytoplasmic LDH occurs. We have now compared this phenomenon in peritoneal leukocytes elicited from animals pretreated in three ways: glycogen, interleukin-1 beta (IL-1 beta) alone or glycogen plus IL-1 beta. Peritoneal administration of IL-1 beta caused elicitation of cells which were enriched in eosinophils; however, the functional responses of the cells in all three groups were broadly similar in terms of the ability of the agonists FMLP, PMA and A23187 to initiate superoxide generation, beta-glucuronidase secretion and leukotriene generation. Cells from all three treatment groups showed diminished responsiveness at 10(-5) M A23187, indicative of calcium overload toxicity. This was most evident for the superoxide and beta-glucuronidase responses. Some quantitative differences observed between treatment groups may reflect the different sensitivities of the various cells contained in the mixed leukocyte preparations. We conclude that IL-1 beta induces leukocyte emigration into the peritoneal cavity but that the cell population is different from that induced by glycogen. However, the cells retain susceptibility to calcium overload toxicity.
Charalambous
K
K
Pharmacology Group, King's College, London, U.K.
de las Heras
B
B
Hoult
J R
JR
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D005966:Glucuronidase / Q000378:metabolism; D006003:Glycogen / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D015289:Leukotrienes; D011994:Recombinant Proteins; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium