Premium
The attenuation of leukocyte‐endothelial interactions by a unique broad‐spectrum protein kinase C inhibitor (Gö 6983) in rat mesenteric postcapillary venules
Author(s) -
Chen Qian,
Rueter Brian,
Young Lindon Howard
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.7
Subject(s) - protein kinase c , intravital microscopy , chemistry , nitric oxide , microcirculation , nitric oxide synthase , in vivo , superoxide , biochemistry , pharmacology , kinase , microbiology and biotechnology , medicine , enzyme , biology , organic chemistry
Protein kinase C (PKC) is a very important enzyme that regulates endothelial and leukocyte function. However, the role of broad‐spectrum PKC inhibition involving the atypical zeta isoform in regulating leukocyte‐endothelial interactions has not been clarified in vivo in real‐time. The microcirculation of postcapillary venules in rat mesentery was observed by intravital microscopy. We found that superfusion of N G ‐nitro‐L‐arginine methyl ester (L‐NAME, a nitric oxide synthase (NOS) inhibitor, 50 µM, n=10) significantly increased leukocyte rolling, adherence and transmigration within a 2 hour period compared to superfusion of Krebs' buffer (n=8) (P<0.01). By contrast, in the presence of Gö 6983 (25 nM, n=5/ 100 nM, n=5/ 200 nM, n=6), a unique broad‐spectrum inhibitor of PKC that inhibits isoforms from all three biochemical classes, these leukocyte‐endothelial interactions were dose‐dependently attenuated compared to L‐NAME alone (P<0.05). Moreover, Gö 6983 dose‐dependently decreased superoxide release from neutrophils compared to control (P<0.01). In summary, inhibition of endothelial NOS activity (i.e., superfusion of L‐NAME) enhances leukocyte‐endothelial interactions. By contrast, inhibition of PKC can decrease these increased interactions, which may be related to decreasing superoxide release from neutrophils. This study was supported by Center for Chronic Disorders of Aging at PCOM.