Fibrinogen promotes monocyte adhesion via a protein kinase C dependent mechanism.
The accumulation of blood monocytes at sites of predilection of the vessel wall is an early cellular event of atherogenesis. Proteins of the vessel wall may facilitate monocyte adhesion and thus promote their recruitment. It has been shown that the relative content of extracellular fibrinogen increases during lesion development, and this study investigated the contribution of immobilized fibrinogen to monocyte adhesion and the underlying mechanism. Freshly isolated human blood monocytes were cultivated in serum-free RPMI 1640 in tissue culture wells precoated with albumin, fibrinogen, or fibrin. After 16 h the plates were washed and adherent cells enumerated. Immobilized fibrinogen enhanced monocyte adhesion more than 1.9-fold compared to immobilized albumin or fibrin (P < 0.05). Concomitant addition of the protein kinase C (PKC) inhibitors staurosporine or H7 suppressed monocyte adherence to immobilized fibrinogen but exerted no significant effect upon adhesion to any other surface tested. Stimulation of monocytes using phorbol myristate acetate resulted in increased binding of monocytes on fibrinogen but not on bovine serum albumin. When PKC activity was reduced through prolonged incubation with PMA for 16 h, a significant reduction of monocyte adhesion on fibrinogen was observed. Peptides containing RGD sequences, which have been demonstrated to be ligands for certain integrins, did not inhibit monocyte adhesion. The data suggest that fibrinogen promotes monocyte adhesion in vitro by a PKC-dependent mechanism. PKC appears to be important not only for the initial cell adhesion but also for sustained binding of monocytes to fibrinogen.
Kreuzer
J
J
Innere Medizin III, Universität Heidelberg, Germany.
Denger
S
S
Schmidts
A
A
Jahn
L
L
Merten
M
M
von Hodenberg
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000418:Albumins / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D005337:Fibrin / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000418:Albumins; D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; C080501:1-(5-isoquinolinylsulfonyl)-3-methylpiperazine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005337:Fibrin; D005340:Fibrinogen; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate