Lysophosphatidic acid triggers calcium entry through a nonstore-operated pathway in human neutrophils
Lysophosphatidic acid triggers calcium entry through a nonstore-operated pathway in human neutrophils
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DOI：
10.1189/jlb.0704390
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发表时间：
2005-02-01
影响因子：
5.5
通讯作者：
Hauser, CJ
中科院分区：
文献类型：
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作者：
Itagaki, K;Kannan, KB;Hauser, CJ
溶血磷脂酸（LPA）是一种生物活性脂质，其结构类似于1-磷酸鞘氨醇（SIP），并且可以在多种细胞类型中动员Ca 2+。我们最近发现SIP直接通过人多形核中性粒细胞（PMN）中的钙池操纵的钙离子进入（SOCE）通道诱导钙离子进入[1]。因此，我们研究了LPA诱导PMN细胞内Ca 2+动员的机制。外部应用低微摩尔LPA引起剂量依赖性的Ca 2+内流，而不释放Ca 2+存储，而G-蛋白偶联（GPC）LPA受体响应纳摩尔LPA。与100 nM离子霉素诱导的Ca（2+）内流相比，LPA诱导的Ca（2+）内流是累加的，表明LPA诱导的Ca（2+）内流不通过SOCE通道。Ca ~（2+）内流对百日咳毒素对G（i/o）的抑制、U 73122对磷脂酶C的抑制和Y27632对G（12/13）/Rho的抑制具有抗性，所有这些都证明了GPC受体的独立性。Gd ~（3+）、La ~（3+）、Zn ~（2+）或MRS ~（1845）可抑制Ca ~（2+）内流，但Ni ~（2+）或鞘氨醇激酶抑制剂二甲基鞘氨醇对Ca ~（2+）内流无抑制作用。此外，我们发现LPA对中性粒细胞的趋化性没有影响，但它对中性粒细胞的呼吸爆发有刺激作用，并呈剂量-反应关系。这些结果表明，LPA诱导的PMN中的Ca 2+内流通过SOCE通道以外的机制发生，独立于Ca 2+库耗竭和SIP合成，并且LPA诱导的Ca 2+内流的特征在对无机抑制剂的敏感性方面与SIP诱导的内流相似。与SIP不同，LPA对中性粒细胞呼吸爆发具有刺激作用。
Lysophosphatidic acid (LPA) is a bioactive lipid, which is structurally similar to sphingosine 1-phosphate (SIP) and which can mobilize Ca2+ in multiple cell types. We recently showed that SIP induces Ca2+ entry directly through store-operated Ca2+ entry (SOCE) channels in human polymorphonuclear neutrophils (PMN) [1]. We therefore examined the mechanisms by which LPA induces intracellular Ca2+ mobilization in PMN. External application of low micromolar LPA caused dose-dependent Ca2+ influx without releasing Ca2+ stores, whereas G-protein-coupled (GPC) LPA receptors respond to nanomolar LPA. Additive Ca2+ influx by LPA compared with 100 nM ionomycin-induced Ca (2+) influx suggests that LPAinduced Ca2+ influx does not pass through SOCE channels. Ca2+ influx was resistant to inhibition of G(i/o) by pertussis toxin, of phospholipase C by U73122, and of G(12/13)/Rho by Y27632, all demonstrating GPC receptor independence. This Ca (2+) influx was inhibited by Gd3+, La3+, Zn2+, or MRS1845 but not by Ni2+ or the sphingosine kinase inhibitor dimethylsphingosine. In addition, we found that LPA has no effect on neutrophil chemotaxis; however, it has stimulatory effects on neutrophil respiratory burst in a dose-response manner. These findings suggest that LPA-induced Ca2+ influx in PMN occurs through a mechanism other than SOCE channels, independent of Ca2+ storedepletion and SIP synthesis, and that the characteristics of LPA-induced Ca2+ influx are similar to those of SIP-induced influx in terms of sensitivity to inorganic inhibitors. Unlike SIP, LPA has stimulatory effects on neutrophil respiratory burst.