Role of different Ca2+ sources in the superoxide production of human neutrophil granulocytes

• Published in: Free radical biology & medicine Vol. 26; no. 9-10; pp. 1092 - 1099
• Main Authors: Geiszt, M, Szeberényi, J B, Káldi, K, Ligeti, E
• Format: Journal Article
• Language: English
• Published: United States 01.05.1999
• Subjects: Calcium - metabolism; Calcium - pharmacology; Calcium Channels - drug effects; Calcium Channels - metabolism; Calcium-Transporting ATPases - antagonists & inhibitors; Cell Membrane - drug effects; Cell Membrane - metabolism; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Humans; In Vitro Techniques; Ion Transport - drug effects; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; NADPH Oxidases - metabolism; Neutrophils - drug effects; Neutrophils - metabolism; Superoxides - metabolism; Thapsigargin - pharmacology
• ISSN: 0891-5849
• DOI: 10.1016/s0891-5849(98)00283-4

The role of different Ca2+ sources in the activation of the NADPH oxidase was investigated in human neutrophil granulocytes. Selective depletion of the stimulus-responsive intracellular Ca2+ -pool and the consequent opening of the store-dependent Ca2+ channel of the plasma membrane was achieved with thapsigargin, an inhibitor of microsomal Ca2+ -ATPase. Low concentration (10-100 nM) of thapsigargin did not induce any O2*- -production, indicating that elevation of [Ca2+]ic to similar level and probably via similar route as following stimulation of chemotactic receptors, by itself is not sufficient to activate the NADPH oxidase. In significantly higher concentration (1-10 microM) thapsigargin did induce O2*- -generation but this effect was not the result of elevation of [Ca2+]ic. In the absence of external Ca2+ a gradual decrease of the responsive Ca2+ pool was accompanied by a gradual decrease of the rate and duration of the respiratory response stimulated by formyl-methionyl-leucyl-phenylalanin. Maximal extent of receptor-initiated O2*- -production could only be obtained when the intracellular [Ca2+] was higher than the resting level. Under this condition Ca2+ originating from intracellular or external source was equally effective in supporting the biological response.