Premium
Fas activation opposes PMA‐stimulated changes in the localization of PKCδ: a mechanism for reducing neutrophil adhesion to endothelial cells
Author(s) -
Hendey Bill,
Zhu Chun Liu,
Greenstein Stephanie
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.5.863
Subject(s) - rottlerin , protein kinase c , microbiology and biotechnology , adhesion , biology , phorbol , apoptosis , signal transduction , cell adhesion , biochemistry , chemistry , cell , organic chemistry
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 β2 integrins responsible for endothelial adhesion. A possible signaling mechanism for Fas effects on adhesion is the localization of protein kinase C δ (PKCδ). Western blot and immunofluorescence studies indicated that 1 h of Fas activation is required to reduce PMA‐stimulated translocation of PKCδ to the membrane and adhesion. Rottlerin, a PKCδ inhibitor, also reduced PMA‐induced PKCδ translocation and adhesion. In contrast, Gö6976, an inhibitor of conventional PKC isotypes, did not affect PMA‐stimulated PKCδ 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.