J. Kreuzer et al., FIBRINOGEN PROMOTES MONOCYTE ADHESION VIA A PROTEIN-KINASE-C DEPENDENT MECHANISM, Journal of molecular medicine, 74(3), 1996, pp. 161-165
Citations number
25
Categorie Soggetti
Medical Laboratory Technology","Genetics & Heredity
The accumulation of blood monocytes at sites of predilection of the ve
ssel wall is an early cellular event of atherogenesis. Proteins of the
vessel wall may facilitate monocyte adhesion and thus promote their r
ecruitment. It has been shown that the relative content of extracellul
ar fibrinogen increases during lesion development, and this study inve
stigated the contribution of immobilized fibrinogen to monocyte adhesi
on and the underlying mechanism. Freshly isolated human blood monocyte
s were cultivated in serum-free RPMI 1640 in tissue culture wells prec
oated 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 o
r fibrin (P<0.05). Concomitant addition of the protein kinase C (PKC)
inhibitors staurosporine or H7 suppressed monocyte adherence to immobi
lized fibrinogen but exerted no significant effect upon adhesion to an
y other surface tested. Stimulation of monocytes using phorbol myrista
te acetate resulted in increased binding of monocytes on fibrinogen bu
t not on bovine serum albumin. When PKC activity was reduced through p
rolonged incubation with PMA for 16 h, a significant reduction of mono
cyte adhesion on fibrinogen was observed. Peptides containing RGD sequ
ences, which have been demonstrated to be ligands for certain integrin
s, 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 al
so for sustained binding of monocytes to fibrinogen.