The leukocyte integrin Mac-1 (CD11b/CD18) contributes to binding of human granulocytes to collagen.
Adhesion of polymorphonuclear granulocytes (PMN) to extracellular matrix proteins has been shown to be important for their migration in vitro and is thought to participate in PMN recruitment to sites of inflammation. Isolated human PMN stimulated with PMA were found to adhere best to microtiter wells coated with the novel ECM glycoprotein undulin (27 +/- 3% of PMNs added), followed by fibrinogen (25 +/- 2%), collagen type VI (18 +/- 2%), fibronectin (16 +/- 2%), and laminin (15 +/- 3%). PMN adhesion to other collagens ranged between 3 and 11%. Monoclonal antibodies recognizing CD18 and CD11b subunits of Mac-1 inhibited adhesion of PMN to collagens by an order of magnitude more effectively than to all noncollagenous substrates. F(ab')2 fragments of the anti-CD18 antibody were also able to block adhesion to collagens. Anti-LFA-1 (CD11a) and anti-CD44 antibodies did not significantly reduce adhesion. PMN adhesion was also inhibited by soluble collagens type II and VI (ID50 approximately 75 micrograms/ml). Binding of soluble radiolabeled collagens type II and VI to PMNs was specific and saturable with apparent dissociation constants of 2.2 and 1.9 nM, respectively, and specific binding of collagens type II and VI was almost completely inhibited by anti-CD18, but not by control antibodies. These data indicate that Mac-1 function is required for binding of human PMN to collagens.
Walzog
B
B
Department of Physiology, Free University Berlin, Germany.
Schuppan
D
D
Heimpel
C
C
Hafezi-Moghadam
A
A
Gaehtgens
P
P
Ley
K
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018845:CD11 Antigens / Q000276:immunology / Q000502:physiology*; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000302:isolation & purification; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; C054447:COL14A1 protein, human; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D016177:Macrophage-1 Antigen; D003094:Collagen; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate