CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen.
Fibrinogen and fibrin serve as adhesive substrates for a variety of cells including platelets, endothelial cells, and leukocytes. Previously, we identified the C terminus of the gamma chain of fibrinogen as the region of the fibrinogen molecule that contains a ligand for CD11b/CD18 (complement receptor 3) on phorbol ester-stimulated polymorphonuclear leukocytes. In contrast, we report here that neutrophils stimulated with tumor necrosis factor adhere to fibrinogen-coated surfaces, but not to human serum albumin-coated surfaces, via the integrin CD11c/CD18 (p150/95). Monoclonal antibodies LeuM5 and 3.9, which are directed against the alpha subunit of CD11c/CD18, but not monoclonal antibodies OKM10 and OKM1, which are directed against the alpha subunit of CD11b/CD18, inhibit the adhesion of tumor necrosis factor-stimulated neutrophils to fibrinogen-coated surfaces. To identify the site on fibrinogen recognized by CD11c/CD18, we have examined the adhesion of tumor necrosis factor-stimulated neutrophils to surfaces coated with various fibrinogen fragments. Stimulated neutrophils adhere to surfaces coated with the N-terminal disulfide knot fragment of fibrinogen or fibrinogen fragment E. Moreover, peptides containing the sequence Gly-Pro-Arg (which corresponds to amino acids 17-19 of the N-terminal region of the A alpha chain of fibrinogen), and monoclonal antibody LeuM5, block tumor necrosis factor-stimulated neutrophil adhesion to fibrinogen and to the N-terminal disulfide knot fragment of fibrinogen. Thus, CD11c/CD18 on tumor necrosis factor-stimulated neutrophils functions as a fibrinogen receptor that recognizes the sequence Gly-Pro-Arg in the N-terminal domain of the A alpha chain of fibrinogen.
Loike
J D
JD
Columbia University, New York, NY 10032.
Sodeik
B
B
Cao
L
L
Leucona
S
S
Weitz
J I
JI
Detmers
P A
PA
Wright
S D
SD
Silverstein
S C
SC
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018845:CD11 Antigens; D018821:CD18 Antigens; D046911:Macromolecular Substances; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen