Fibrinogen induces chemotactic activity in endothelial cells.
Chemotaxis of blood monocytes into the vessel wall together with the change of the relative content of the extracellular matrix (ECM) proteins at sites of predilection is an early cellular marker of atherogenesis. To examine the influence of ECM proteins on secretion of chemoattractants by endothelial cells (EC), porcine EC were seeded on gelatin (G), fibronectin (Fn) and fibrinogen (Fg). After 24 h cells seeded on G and Fn showed the histiotypic 'cobblestone'-morphology whereas cells seeded on Fg did not. Chemotactic activity for monocytes in supernatants from cells seeded on Fg was more than two-fold higher compared with G and was independent of soluble Fn or Fg in the supernatant. Quantification of monocyte chemoattracting protein-1, PDGF-AB and IL-8 in EC supernatants showed that Fg led to a significant increase in secretion of all three proteins compared with cells cultured on G. Preincubation of porcine EC with the tripeptide arginine-glycine-aspartic acid, as inhibitor of binding of Fg to integrin receptors, but not with the control tripeptide arginine-glycine-glutamic acid showed a decrease in chemotactic activity for cells cultured on Fg but not on Fn or G. Inhibition of protein kinase C (PKC) activity in EC by GF109203 resulted in a decrease of fibrinogen-induced chemotactic activity. Also the tyrosine-kinase inhibitor herbimycin inhibited fibrinogen mediated secretion of chemokines. The role of the PKC pathway for matrix mediated signal transduction is further corroborated by Fg-dependent induction of the PKC isoform delta. These data indicate an integrin-dependent signal transduction pathway leading to induction of chemotactic activity by the ECM protein fibrinogen. This mechanism may contribute to induction of chemokines in early atherosclerotic lesions.
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005340:Fibrinogen / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D005780:Gelatin; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D011493:Protein Kinase C / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D013552:Swine
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005780:Gelatin; D005340:Fibrinogen; D011493:Protein Kinase C