Lysophosphatidic acid opens a Ca(++) channel in human erythrocytes.
Lysophosphatidic acid opens a Ca(++) channel in human erythrocytes.
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DOI：
10.1182/blood.v95.7.2420.007k12_2420_2425
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发表时间：
2000-04
期刊：
影响因子：
20.3
通讯作者：
Lu Yang;Dina A. Andrews;Philip S. Low
中科院分区：
文献类型：
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作者：
Lu Yang;Dina A. Andrews;Philip S. Low
溶血磷脂酸 (LPA) 是一种脂质衍生的第二信使，可动员循环和血管系统的许多细胞来协助血栓形成和伤口愈合。然而，LPA 尚未在人类红细胞上进行过测试，主要是因为红细胞被认为具有生物惰性并且在细胞间通讯中不活跃。为了验证这一假设，我们研究了 LPA 对人红细胞 (RBC) 内信号反应的影响。使用 (45)Ca(++) 和 Ca(++) 敏感荧光探针 (Fluo-3)，我们证明 LPA（而不是磷脂酸或密切相关的 1-磷酸鞘氨醇）刺激微摩尔量的细胞外 Ca(++) 流入新鲜红细胞。这种 Ca(++) 流入被证明是通道介导的而不是促进泄漏，因为在 LPA 浓度太低而无法扰乱膜完整性时观察到流入，它被 P 型但不是 L 型 Ca(++) 通道阻滞剂抑制，它被广泛特异性蛋白激酶抑制剂抑制，并且它不是由 LPA 的无活性类似物诱导的。进一步的表征表明，只有大约 25% 的红细胞参与 LPA 诱导的 Ca(++) 进入，并且在该活跃群体中，Ca(++) 门控以全有或全无的方式发生。由于 Ca(++) 吸收的刺激发生在已知发生在正在形成的血栓附近的 LPA 浓度 (1-5 µmol/L) 下，并且由于内化的 Ca(++) 可能会促进受刺激的红细胞中的促血栓特性，因此我们得出结论，红细胞对其他细胞释放的信号并非不敏感。
Lysophosphatidic acid (LPA) is a lipid-derived second messenger that mobilizes many cells of the circulatory and vascular systems to assist in thrombus development and wound healing. LPA, however, has not been tested on human erythrocytes, largely because erythrocytes are considered to be both biologically inert and inactive in intercellular communication. To test this presumption, we have examined the impact of LPA on signaling reactions within the human red blood cell (RBC). Using both (45)Ca(++) and a Ca(++)-sensitive fluorescent probe (Fluo-3), we demonstrated that LPA, but not phosphatidic acid or the closely related sphingosine-1-phosphate, stimulates the influx of micromolar quantities of extracellular Ca(++) into fresh RBCs. This Ca(++) influx was shown to be channel mediated rather than leak promoted because the influx was observed at LPA concentrations too low to perturb membrane integrity, it was inhibited by P-type but not L-type Ca(++) channel blockers, it was inhibited by broad-specificity protein kinase inhibitors, and it was not induced by inactive analogues of LPA. Further characterization reveals that only approximately 25% of the RBCs participate in LPA-induced Ca(++) entry and that within this active population, Ca(++) gating occurs in an all-or-nothing manner. Because the stimulation of Ca(++) uptake occurs at LPA concentrations (1-5 micromol/L) known to occur near a developing thrombus and because the internalized Ca(++) can potentially promote prothrombic properties in the stimulated RBCs, we conclude that RBCs are not insensitive to signals released from other cells.