Involvement of ion channels in human eosinophil respiratory burst.
BACKGROUND: Human eosinophils possess a variety of ion channels that play a crucial role in the regulation of cellular activity. During eosinophil respiratory burst, efflux of H(+) ions through H(+) channels provides an efficient mechanism of H(+) extrusion and charge compensation. Interestingly, recent studies suggest that other ion channels may also be involved in this process. OBJECTIVE: We sought to investigate the role of ion channels in phorbol 12-myristate 13-acetate-induced superoxide (O(2)(*-)) generation by human eosinophils. METHODS: O(2)(*-) production was measured by using the superoxide dismutase-inhibitable reduction of cytochrome c. Ion channel expression and function were studied by using RT-PCR and the patch clamp technique, respectively. RESULTS: O(2)(*-) generation was affected by several ion channel blockers, especially 4,4-diisothio-cyanostilbene-2,2'-disulfonic acid. The involvement of Cl(-) channels in this process was confirmed by replacement of Cl(-) with gluconate or other anions. The halide dependence of O(2)(*-) production could be described by the sequence Cl(-)> or =Br(-)>I(-), which is similar to the selectivity sequence of several members of the chloride channel (ClC) family. RT-PCR studies performed with primers for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6, and the cystic fibrosis transmembrane conductance regulator showed only the expression of ClC-3. The presence of phorbol 12-myristate 13-acetate-sensitive Cl(-) channels in human eosinophils with biophysical properties similar to the ClC-3 channel has been studied. CONCLUSION: Cl(-) channels play an important role in the regulation of O(2)(*-) production by human eosinophils.[1]References
- Involvement of ion channels in human eosinophil respiratory burst. Schwingshackl, A., Moqbel, R., Duszyk, M. J. Allergy Clin. Immunol. (2000) [Pubmed]
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