Itagaki Kiyoshi, Kannan K B, Livingston David H, Deitch Edwin A, Fekete Zoltan, Hauser Carl J
Department of Surgery, Division of Trauma, New Jersey Medical School, Newark, NJ 07103, USA.
J Immunol. 2002 Apr 15;168(8):4063-9. doi: 10.4049/jimmunol.168.8.4063.
Human polymorphonuclear neutrophil (PMN) responses to G protein-coupled chemoattractants are highly dependent upon store-operated Ca(2+) entry (SOCE). Recent research suggests that SOCE currents can be mediated by a variety of related channel proteins of the transient receptor potential superfamily. SOCE has been regarded as a specific response to depletion of cell calcium stores. We hypothesized that net SOCE might reflect the contributions of more than one calcium entry pathway. SOCE was studied in normal human PMN using Ca(2+) and Sr(2+) ions. We found that PMN SOCE depends on at least two divalent cation influx pathways. One of these was nonspecific and Sr(2+) permeable; the other was Ca(2+) specific. The two pathways show different degrees of dependence on store depletion by thapsigargin and ionomycin, and differential sensitivity to inhibition by 2-aminoethyoxydiphenyl borane and gadolinium. The inflammatory G protein-coupled chemoattractants fMLP, platelet-activating factor, and IL-8 elicit unique patterns of Sr(2+) and Ca(2+) influx channel activation, and SOCE responses to these agonists displayed differing degrees of linkage to prior Ca(2+) store depletion. The mechanisms of PMN SOCE responses to G protein-coupled chemoattractants are physiologically diverse. They appear to reflect Ca(2+) transport through a variety of channels that are independently regulated to varying degrees by store depletion and by G protein-coupled receptor activation.
人类多形核中性粒细胞（PMN）对G蛋白偶联趋化因子的反应高度依赖于储存-操作性钙（Ca2+）内流（SOCE）。最近的研究表明，SOCE电流可由瞬时受体电位超家族的多种相关通道蛋白介导。SOCE一直被视为对细胞钙储存耗竭的一种特异性反应。我们推测，净SOCE可能反映了不止一种钙内流途径的作用。我们使用Ca2+和Sr2+离子在正常人PMN中研究了SOCE。我们发现PMN的SOCE依赖于至少两种二价阳离子内流途径。其中一种是非特异性的且可通透Sr2+；另一种对Ca2+具有特异性。这两种途径对毒胡萝卜素和离子霉素引起的储存耗竭表现出不同程度的依赖性，并且对2-氨基乙氧基二苯硼烷和钆的抑制作用具有不同的敏感性。炎症性G蛋白偶联趋化因子fMLP、血小板活化因子和IL-8引发独特的Sr2+和Ca2+内流通道激活模式，并且对这些激动剂的SOCE反应显示出与先前Ca2+储存耗竭不同程度的关联。PMN对G蛋白偶联趋化因子的SOCE反应机制在生理上是多样的。它们似乎反映了Ca2+通过多种通道的转运，这些通道在不同程度上受到储存耗竭和G蛋白偶联受体激活的独立调节。
