AGGREGATION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES BY ENDOTHELIN - ROLE OF PLATELET-ACTIVATING-FACTOR

被引:67
作者
GOMEZGARRE, D [1 ]
GUERRA, M [1 ]
GONZALEZ, E [1 ]
LOPEZFARRE, A [1 ]
RIESCO, A [1 ]
CARAMELO, C [1 ]
ESCANERO, J [1 ]
EGIDO, J [1 ]
机构
[1] UNIV AUTONOMA MADRID, FDN JIMENEZ DIAZ, NEFROL LAB, AVE REYES CATOLICOS S, E-28040 MADRID, SPAIN
关键词
ENDOTHELIN; AGGREGATION; POLYMORPHONUCLEAR LEUKOCYTES; PAF(PLATELET-ACTIVATING FACTOR; PAF-ACETHER);
D O I
10.1016/0014-2999(92)90801-A
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The mechanisms by which endothelin-I (ET-1) acts on polymorphonuclear leukocytes (PMN) are insufficiently known. In this study, we assessed the hypotheses that ET-1 is a PMN-aggregating agent, and that platelet-activating factor (PAF) is the principal mediator of ET-1-induced PMN aggregation. ET-1 induced dose-related PMN aggregation, which started 1 min after ET-1 exposure. Two different specific PAF receptor antagonists blocked the effect of ET-1 on PMN aggregation. In addition, ET-1 induced a significant increase in the production of PAF by PMN after 2 to 5 min of ET-1 incubation. ET-1 induced PAF release from PMN rather than accumulation. This PAF production was dependent on intra- and extracellular Ca2+. In this regard, the PAF receptor antagonists significantly blunted the ET-1-induced peak in cytosolic free Ca2+([Ca2+]i). Our results, therefore, indicate that ET-1 is effective in causing aggregation of human PMN and that its action appears to be mediated by PAF production via a Ca2+-dependent mechanism.
引用
收藏
页码:167 / 172
页数:6
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