Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway.
Leukocyte traffic in immune-inflammatory responses requires regulated adhesion of leukocyte subsets to vascular endothelium. We show that fibrinogen or normal human plasma enhances by 2- to 5-fold the adhesion of cells of myeloid and lymphoid lineage to endothelium. This mechanism is mediated by fibrinogen binding to complementary membrane receptors on leukocytes and endothelial cells. Using an affinity chromatography purification strategy, genetically engineered transfectants, and direct binding studies to the isolated recombinant protein, we identified a novel hematopoietic fibrinogen receptor participating in this adhesion pathway as intercellular adhesion molecule 1 (ICAM-1). Accordingly, a new model can be proposed, in which fibrinogen binding to a variety of vascular cell receptors mediates a specific pathway of cell to cell adhesion by bridging together leukocytes and endothelial cells.
Languino
L R
LR
Scripps Research Institute, La Jolla, California 92037.
Plescia
J
J
Duperray
A
A
Brian
A A
AA
Plow
E F
EF
Geltosky
J E
JE
Altieri
D C
DC
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D001667:Binding, Competitive; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen