Rediske J, Morrissey M M, Jarvis M
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
Cell Immunol. 1993 Apr 1;147(2):438-45. doi: 10.1006/cimm.1993.1082.
To define the intracellular activation events stimulated by leukotriene B4 (LTB4) in human monocytes, we investigated the transient increase in cytosolic free calcium levels ([Ca2+]i) elicited by this lipid mediator. Using elutriated human monocytes, LTB4 caused a dose-dependent increase in [Ca2+]i with an ED50 of 1.0 nM. The LTB4-induced [Ca2+]i response exhibited ligand selectivity, with both the diastereomer 5S-12S-diHETE and the 20-COOH LTB4 inactive at 500 nM, while 20-OH LTB4 was a partial agonist with an approximate ED50 of 10 nM. This response demonstrated stimulus-specific deactivation and was inhibited by the specific LTB4 receptor antagonist LY-223982. These results suggest that LTB4 stimulated an increase in [Ca2+]i via interaction with a defined LTB4 receptor. The inhibitory effects of pertussis toxin and PMA on the LTB4-induced [Ca2+]i suggest that a receptor-linked guanine nucleotide-binding protein and protein kinase C are involved in the regulation of the LTB4-elicited increase in [Ca2+]i. The LTB4-induced cell activation event may play a key role in the functional responses elicited by LTB4 in human monocytes.
为了确定白三烯B4（LTB4）在人单核细胞中刺激的细胞内激活事件，我们研究了这种脂质介质引起的胞质游离钙水平（[Ca2+]i）的短暂升高。使用淘洗过的人单核细胞，LTB4引起[Ca2+]i呈剂量依赖性增加，ED50为1.0 nM。LTB4诱导的[Ca2+]i反应表现出配体选择性，非对映异构体5S-12S-二氢二十碳四烯酸（diHETE）和20-COOH LTB4在500 nM时均无活性，而20-OH LTB4是一种部分激动剂，近似ED50为10 nM。该反应表现出刺激特异性失活，并被特异性LTB4受体拮抗剂LY-223982抑制。这些结果表明，LTB4通过与特定的LTB4受体相互作用刺激[Ca2+]i升高。百日咳毒素和佛波酯（PMA）对LTB4诱导的[Ca2+]i的抑制作用表明，一种受体偶联的鸟嘌呤核苷酸结合蛋白和蛋白激酶C参与了LTB4引起的[Ca2+]i升高的调节。LTB4诱导的细胞激活事件可能在LTB4在人单核细胞中引发的功能反应中起关键作用。
