Interferon-gamma induction of LFA-1-mediated homotypic adhesion of human monocytes.
Cell-cell adhesion plays an important role in monocyte function. To investigate the molecular basis for monocyte adhesion, we used recombinant interferon-gamma to induce the formation of homotypic monocyte adhesions. The induction of homotypic adhesions correlated with the increased expression of the LFA-1 membrane molecule. LFA-1 surface expression was increased twofold, whereas expression levels of other monocyte surface molecules including CR3 and p150,95 were unchanged. The direct involvement of LFA-1 in monocyte adhesion was addressed by anti-LFA-1 monoclonal antibody inhibition of homotypic adhesions. Two monoclonal antibodies to distinct epitopes on the LFA-1 alpha-chain completely inhibited homotypic adhesions. Antibodies to a variety of other monocyte surface molecules, often present at higher cell surface density than LFA-1, did not inhibit homotypic adhesion. A panel of monoclonal antibodies that recognized different functional epitopes on the LFA-1 alpha-chain inhibited homotypic monocyte in a hierarchy identical to that observed in previous studies of cell-mediated cytotoxicity. These findings suggest that LFA-1 serves an adhesive function for human mononuclear phagocytes. In addition to providing a molecular basis for homotypic monocyte adhesions, the results suggest a more general role for LFA-1 in monocyte adhesion reactions.
S J
SJ
Mentzer
D V
DV
Faller
S J
SJ
Burakoff
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D007371:Interferon-gamma