Itraconazole antagonizes store-operated influx of calcium into chemoattractant-activated human neutrophils.
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| Abstract |
We have investigated the effects of itraconazole (0.1-10 micro m), an antimycotic which is often used prophylactically in primary and secondary immunodeficiency disorders, including chronic granulomatous disease, on mobilization of Ca(2+) and restoration of Ca(2+) homeostasis following activation of neutrophils with FMLP or PAF. Transmembrane fluxes of Ca(2+), as well as cytosolic concentrations of the cation were measured using a combination of spectrofluorimetric and radiometric procedures. The abruptly occurring increases in cytosolic Ca(2+) following activation of the cells with either FMLP (1 micro m) or PAF (200 nm) were unaffected by itraconazole. However, the subsequent store-operated influx of the cation was attenuated by itraconazole at concentrations of 0.25 micro m and higher. The itraconazole-mediated inhibition of uptake of Ca(2+) was not associated with detectable alterations in the intracellular concentrations of cyclic AMP, ATP or inositol triphosphate, and appeared to be compatible with antagonism of store-operated Ca(2+) channels. Although a secondary property, this anti-inflammatory activity of itraconazole, if operative in vivo, may be beneficial in conditions associated with dysregulation of neutrophil Ca(2+) handling such as CGD.
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| Authors | H C Steel, R Anderson |
| Journal | Clinical and experimental immunology (Clin Exp Immunol) Vol. 136 Issue 2 Pg. 255-61 (May 2004) ISSN: 0009-9104 [Print] England |
| PMID | 15086388 (Publication Type: Journal Article) |
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