title: Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells.
abstract: It has been reported that fibrinogen may act as a bridging ligand, binding to intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells and to Mac-1 on THP-1 cells (a monocytic cell line) to increase adhesion. In this study, we investigated whether fibrinogen altered the expression of ICAM-1 and, thus, increased the adhesion of THP-1 cells to cultured human saphenous vein endothelial cells (HSVECs). Incubation of HSVECs with 0.3 to 4 micromol/L fibrinogen caused a time- and concentration-dependent increase in ICAM-1, as determined by ELISA. The 4- to 5-fold increase in ICAM-1 protein concentration in HSVECs stimulated by 4 micromol/L fibrinogen for 6 hours was concomitant with a 4- to 5-fold increase in ICAM-1 mRNA. This fibrinogen-stimulated ICAM-1 upregulation was associated with a 2-fold increase in THP-1 cell adhesion to HSVECs. The fibrinogen-derived peptide Bbeta15-42 bound to HSVECs (K(d) 0.18 micromol/L). Preincubation of HSVECs with Bbeta15-42, a neutralizing antibody to urokinase plasminogen activator (uPA), or the F(ab)(1) fragment of a monoclonal antibody to vascular endothelial cadherin significantly attenuated the increase in ICAM-1 stimulated by fibrinogen. Capillary electrophoretic analysis indicated that anti-uPA prevented the release of any fibrinopeptide B (Bbeta1-14) in cultures of HSVECs incubated with 4 micromol/L fibrinogen for 6 hours. Moreover, incubation of HSVECs with either fibrin monomer (1 micromol/L) or monoclonal antibodies to vascular endothelial cadherin (25 microg/mL) increased ICAM-1 protein concentration 3- to 4-fold. These findings indicate that cleavage of fibrinopeptide B from fibrinogen by endothelial uPA permits the exposed Bbeta15-42 sequence of fibrinogen to bind to vascular endothelial cadherin on HSVECs and to upregulate the expression of ICAM-1.
authors.affiliation: Department of Vascular Surgery, Imperial School of Medicine at Charing Cross Hospital, London, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Harley
authors.forename: J
authors.initials: J
authors.lastname: Sturge
authors.forename: J T
authors.initials: JT
authors.lastname: Powell
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012501:Saphenous Vein / Q000166:cytology; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology; D000099152:Cadherin 5
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015820:Cadherins; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D018799:Intercellular Adhesion Molecule-1; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator; D000099152:Cadherin 5; C033786:fibrinogen Bbeta (15-42)