Modulation of endothelial cell expression of intercellular adhesion molecule 1 by protein kinase C activation.
Inflammatory stimuli enhance the adherence properties of human umbilical vein endothelial cells (HUVEC) for neutrophils (PMN). This is mediated in part by the up-regulation on HUVEC of Intercellular Adhesion Molecule 1 (ICAM 1). Phorbol esters, which activate protein kinase c (PKC), have also been reported to enhance the adherence properties of HUVEC for PMN. We investigated the effect of agents which activate PKC on the expression of ICAM 1 by HUVEC. Both phorbol myristate acetate (PMA) and Mezerein, a non-phorbol which also stimulates PKC, enhanced both the expression of ICAM 1 on HUVEC and the adherence of HUVEC for PMN. The PKC inhibitors staurosporine and H-7 prevented both PMA and Mezerein-induced stimulation of HUVEC expression of ICAM 1 and adherence for PMN. We conclude that activation of PKC in HUVEC is associated with increased expression of ICAM 1 on HUVEC. PKC-mediated up-regulation of ICAM 1 may be responsible, in part, for the promotion of endothelial cell adherence properties toward PMN.
Lane
T A
TA
V A Medical Center, San Diego, CA.
Lamkin
G E
GE
Wancewicz
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000954:Antigens, Surface / Q000032:analysis*; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D004224:Diterpenes; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D019311:Staurosporine; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D000954:Antigens, Surface; D002273:Carcinogens; D015815:Cell Adhesion Molecules; D004224:Diterpenes; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D010879:Piperazines; D013729:Terpenes; C008875:phorbol-12,13-dibenzoate; C011309:mezerein; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate