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

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 β 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 (IClvol) suggesting that IClvol 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 IClvol 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 β 2 integrin up-regulation. However, ethacrynic acid, at the same concentration that inhibits activator-induced Cl- efflux and up-regulation, had no effect on IClvol and swelling-activated Cl - efflux, providing evidence against the involvement of I Clvol in the activator-induced Cl- efflux.

5 nitro 2 (3 phenylpropylamino)benzoic acid; beta2 integrin; cell adhesion molecule; chloride channel; chloride channel blocking agent; etacrynic acid; hypotonic solution; phenol derivative; unclassified drug; [3 methyl 1 (4 sulfophenyl) 5 pyrazolone (4)](1,3 dibutylbarbituric acid)pentamethine oxonol; article; binding affinity; cell adhesion; cell strain HL 60; cell swelling; cell volume; chloride transport; concentration response; controlled study; human; human cell; inflammation; leukocyte activation; neutrophil; patch clamp; priority journal; protein expression; venule

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