ANION CHANNEL BLOCKERS INHIBIT LYSOSOMAL ENZYME-SECRETION FROM HUMAN-NEUTROPHILS WITHOUT AFFECTING GENERATION OF SUPEROXIDE ANION
ANION CHANNEL BLOCKERS INHIBIT LYSOSOMAL ENZYME-SECRETION FROM HUMAN-NEUTROPHILS WITHOUT AFFECTING GENERATION OF SUPEROXIDE ANION
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DOI：
10.1073/pnas.77.5.2721
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
WEISSMANN, G
中科院分区：
文献类型：
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作者：
KORCHAK, HM;EISENSTAT, BA;WEISSMANN, G
用阴离子通道阻断剂4，4“-二异硫氰基芪-2，2”-二磺酸（DIDS）、4-乙酰氨基-4“-异硫氰基芪-2，2 "-二磺酸（SITS）和磷酸吡哆醛研究了渗透性阴离子对人中性粒细胞溶酶体酶分泌的作用。在抑制硫酸盐通量的浓度下，DIDS、SITS和磷酸吡哆醛抑制了经细胞松弛素B处理的人中性粒细胞在免疫复合物（牛血清白蛋白和抗牛血清白蛋白的IG[免疫球蛋白]G）刺激下的溶酶体酶释放。由钙离子载体A23187引发的酶分泌也被抑制DIDS和SITS;这些试剂作用于Ca 2+流入后的分泌事件。无论是渗透阴离子的种类（S），也没有在脱粒的阴离子通量的作用被确定，虽然氯离子，氢氧化物或磷酸根离子的流入并不关键。与脱粒相反，超氧阴离子（O2.-）免疫复合物或A23187刺激的细胞增殖不受这些药物的抑制。超微结构细胞化学研究表明，虽然溶酶体内容物没有从刺激的细胞中排出，空泡形成和溶酶体融合不受SITS或DIDS的影响。显然阴离子通道阻断剂特异性地抑制溶酶体与质膜的融合或其内陷。
The role of permeant anions in lysosomal enzyme secretion from human neutrophils was investigated by means of anion-channel-blocking agents: 4,4''-diisothiocyanostilbene-2,2''-disulfonic acid (DIDS), 4-acetamido-4''-isothiocyanostilbene-2,2''-disulfonic acid (SITS) and pyridoxal phosphate. Lysosomal enzyme release from cytochalasin B-treated human neutrophils stimulated by immune complexes (bovine serum albumin and Ig[immunoglobulin]G anti-bovine serum albumin) was inhibited by DIDS, SITS and pyridoxal phosphate at concentrations that inhibited sulfate fluxes. Enzyme secretion triggered by calcium ionophore A23187 was also inhibited by DIDS and SITS; these agents acted on secretory events subsequent to Ca2+ influx. Neither the species of permeant anion(s) nor the role of anion fluxes in degranulation was identified, although influxes of Cl, hydroxide or phosphate ions were not critical. In contrast to degranulation, generation of superoxide anions (O2.-) stimulated by immune complex or A23187 was not inhibited by these agents. Ultrastructural cytochemcial studies demonstrated that although lysosomal contents were not discharged from stimulated cells, vacuole formation and lysosome-lysosome fusion were unaffected by SITS or DIDS. Apparently anion channel blockers specifically inhibit fusion of lysosomes with the plasma membrane or its invaginations.