MAC-1 mediates adherence of human monocytes to endothelium via a protein kinase C dependent mechanism.
Leukocyte adherence is mediated by a superfamily of glycoproteins denoted LFA-1 (the lymphocyte function-associated antigen-1), Mac-1 (macrophage antigen-1) and p150,95. The relative importance of these in mediating human monocyte adherence to endothelium, and the biochemical mechanisms which modulate these events, are not understood. In this report, the role of protein kinase C (pkC) in regulating human monocyte adherence to endothelial cells has been investigated. Addition of phorbol 12,13-dibutyrate (PDBu), which specifically stimulates pkC, caused a dose-dependent increase in their adherence to monolayers of bovine aortic endothelial cells. 4 alpha-phorbol didecanoate (4 alpha-PDD), a structural analogue of PDBu which does not stimulate pkC, failed to increase monocyte adhesion. PDBu also produced a dose-dependent increase in the expression of both Mac-1 and p150,95. The pkC-stimulated adherence of monocytes to endothelium was inhibited by the presence of a monoclonal antibody to Mac-1, while monoclonal antibodies to p150,95 and LFA-1 did not influence adherence. It is concluded that monocyte adherence to endothelial cells is regulated through a pkC-dependent mechanism; moreover, this process is mediated primarily via the Mac-1 adhesion glycoprotein.
Gladwin
A M
AM
Wellcome Research Laboratories, Beckenham, U.K.
Hassall
D G
DG
Martin
J F
JF
Booth
R F
RF
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001011:Aorta; D002417:Cattle; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000097:blood*; D016028:Receptors, Leukocyte-Adhesion
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D016028:Receptors, Leukocyte-Adhesion; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C