Fas activation opposes PMA-stimulated changes in the localization of PKCdelta: a mechanism for reducing neutrophil adhesion to endothelial cells.
We have shown previously that Fas activation results in a partial reduction of phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophil adhesion to endothelial cells. The reduction in adhesion precedes early membrane markers of apoptosis and is not associated with any loss of membrane integrity. Rather, Fas activation reduces the PMA-stimulated expression and aggregation of beta2 integrins responsible for endothelial adhesion. A possible signaling mechanism for Fas effects on adhesion is the localization of protein kinase C delta (PKCdelta). Western blot and immunofluorescence studies indicated that 1 h of Fas activation is required to reduce PMA-stimulated translocation of PKCdelta to the membrane and adhesion. Rottlerin, a PKCdelta inhibitor, also reduced PMA-induced PKCdelta translocation and adhesion. In contrast, Gö6976, an inhibitor of conventional PKC isotypes, did not affect PMA-stimulated PKCdelta translocation or reduce adhesion. There was no additive effect of Fas activation and rottlerin on reducing adhesion, suggesting that both agents were using a common pathway.
Hendey
Bill
B
Department of Pharmacology, Rush University, 2242 W. Harrison, Room 264, Chicago, IL 60612, USA. bhendey@rush.edu
Zhu
Chun Liu
CL
Greenstein
Stephanie
S
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004727:Endothelium / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051745:Protein Kinase C-delta; D021381:Protein Transport / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism*
D000098:Acetophenones; D001578:Benzopyrans; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D019014:fas Receptor; C081021:Go 6976; C085746:rottlerin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate