Volume-sensitive chloride channels do not mediate activation-induced chloride efflux in human neutrophils.

Patricia Perez-Cornejo, Jorge Arreola, Foon-Yee Law, Joanne B Schultz, Philip A Knauf

Department of Biochemistry and Biophysics, School of Medicine, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA.

Journal of immunology (Baltimore, Md. : 1950) 2004 Jun 1

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Many agents that activate neutrophils, enabling them to adhere to venular walls at sites of inflammation, cause a rapid Cl(-) efflux. This Cl(-) efflux and the increase in the number and affinity of beta(2) integrin surface adhesion molecules (up-regulation) are all inhibited by ethacrynic acid and certain aminomethyl phenols. The effectiveness of the latter compounds correlates with their inhibition of swelling-activated Cl(-) channels (I(Clvol)), suggesting that I(Clvol) mediates the activator-induced Cl(-) efflux. To test this hypothesis, we used whole-cell patch clamp in hypotonic media to examine the effects of inhibitors of up-regulation on I(Clvol) in neutrophils and promyelocytic leukemic HL-60 cells. Both the channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid and [3-methyl-1-p-sulfophenyl-5-pyrazolone-(4)]-[1,3-dibutylbarbituric acid]-pentamethine oxonol (WW781), a nonpenetrating oxonol, inhibited I(Clvol) at concentrations similar to those that inhibit beta(2) integrin up-regulation. However, ethacrynic acid, at the same concentration that inhibits activator-induced Cl(-) efflux and up-regulation, had no effect on I(Clvol) and swelling-activated Cl(-) efflux, providing evidence against the involvement of I(Clvol) in the activator-induced Cl(-) efflux.

Citation

Patricia Perez-Cornejo, Jorge Arreola, Foon-Yee Law, Joanne B Schultz, Philip A Knauf. Volume-sensitive chloride channels do not mediate activation-induced chloride efflux in human neutrophils. Journal of immunology (Baltimore, Md. : 1950). 2004 Jun 1;172(11):6988-93