Recombinant interleukin-8 induces changes in cytosolic Ca2+ in human neutrophils.
Activation of polymorphonuclear leukocytes (PMNL) by most soluble stimulants is associated with a marked increase in cytosolic free Ca2+ ([Ca2+]i). Interleukin-8 (IL-8), a monocyte-derived neutrophil chemotactic factor and potent neutrophil-activating cytokine, effectively enhanced the resting free [Ca2+]i within human PMNL in a dose-dependent manner (maximal effect with 100 ng/mL). The increase in [Ca2+]i was substantially (55%) inhibited in the absence of extracellular Ca2+. Thus, the increase was due to extra- and intracellular cooperative mobilization of Ca2+, as supported by the reduced effect of IL-8 on [Ca2+]i after quenching with Mn2+. Granulocyte-macrophage colony-stimulating factor and interferon-gamma failed to induce a change in [Ca2+]i, suggesting that they may operate through different signal pathways. Pretreatment with Bordetella pertussis toxin largely inhibited the IL-8-induced change in [Ca2+]i. Thus, IL-8-induced cooperative mobilization of intra- and extracellular Ca2+ leads to a net Ca2+ influx into the cytoplasm through a process mediated by a guanosine triphosphate-binding protein.
Liu
J H
JH
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Blanchard
D K
DK
Wei
S
S
Djeu
J Y
JY
D002118:Calcium / Q000097:blood*; D002712:Chlorides; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D002712:Chlorides; D016209:Interleukin-8; D017895:Manganese Compounds; D011994:Recombinant Proteins; D008345:Manganese; D004533:Egtazic Acid; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C025340:manganese chloride; D002118:Calcium; D016257:Fura-2