Activation of monocytic cells by monoclonal antibodies to the CD11a/18 (LFA-1) complex: mediation by Fc receptor.
IgG1 antibodies reacting with several monocytic antigens form a bridge between the specific antigen and the Fc receptors also expressed on these cells. This results in calcium mobilization and generation of superoxide. Single IgG1 antibodies reacting with the CD11a/CD18 cellular adhesion molecular complex do not, however, induce monocytic activation. This is not because they induce a negative signal, as the response to formyl-methionyl-leucyl2-phenylalanine (FMLP) or direct cross-linking of FcRII is not inhibited. Furthermore, a combination of an intact CD11a and CD18 antibody does induce a rise in intracellular calcium and production of superoxide. This activation is dependent on the binding of the Fc portion of both antibodies to Fc receptors, as F(ab')2 fragments do not cause activation. This suggests that simultaneous binding of opsonized bacteria to cellular adhesion molecules and to Fc receptors on monocytes would facilitate activation of these cells. Furthermore, it illustrates the importance of using F(ab')2 fragments in the analysis of signal transduction molecules on Fc receptor-bearing cells.
Department of Haematology, Middlesex, London.
E A
EA
Macintyre
P J
PJ
Roberts
R
R
Abdul-Gaffar
J
J
Morgan
D C
DC
Linch
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D007140:Immunoglobulin Fab Fragments; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D016028:Receptors, Leukocyte-Adhesion; D002118:Calcium