Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen.
Human polymorphonuclear leukocytes (PMN) have previously been shown to bind to aggregates of fibrin and to fibrinogen-coated surfaces. During their interactions with fibrinogen-coated surfaces, PMN make such close contact with the surface that a portion of the secreted elastase activity is protected from macromolecular protease inhibitors in the surrounding medium. Here we show that the receptor on PMN that mediates this interaction is complement receptor type 3 (CR3; CD11b/CD18), a molecule previously identified as a receptor for the complement protein fragment C3bi. Monoclonal antibodies against CR3 that block the binding of C3bi also block the binding of PMN to fibrinogen-coated surfaces and the formation of a protected compartment. The region of fibrinogen recognized by CR3 lies at the carboxyl terminus of the gamma chain, since peptides based on this sequence effectively inhibit the binding of PMN to fibrinogen-coated surfaces. These peptides also block the binding of C3bi-coated erythrocytes to CR3, thus indicating that a single binding site is used for binding both C3bi and fibrinogen. Sequence analysis shows strong structural similarity between this region of fibrinogen and other known ligands of CR3. These studies thus indicate that CR3 functions as a receptor not only for C3bi but also for fibrinogen.
Wright
S D
SD
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Weitz
J I
JI
Huang
A J
AJ
Levin
S M
SM
Silverstein
S C
SC
Loike
J D
JD
D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002448:Cell Adhesion; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*; D017463:Receptors, Complement 3b
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D010455:Peptides; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D005340:Fibrinogen; D010196:Pancreatic Elastase