Role of CD18 in lymphokine activated killer (LAK) cell-mediated lysis of human monocytes: comparison with other LAK targets.
The role of CD18, identified as the beta chain of the CD11 family of adhesion glycoproteins, in the lysis of normal autologous monocytes by interleukin-2-activated killer (LAK) cells was explored. The addition of several preparations of anti-CD18 monoclonal antibodies (MAbs) to the incubation mixture of LAK cells and various target cells indicated that lysis of autologous monocytes, K562 erythroleukemia tumor cells, FMEX melanoma tumor cells, and fresh ovarian tumor cells were readily inhibited by all anti-CD18 antibodies tested. Kinetic experiments demonstrated that significant inhibition of lysis occurred if RH1-38 antibody was added up to 2 hr after LAK cells were added to target cells. By the use of selective coating of targets and effector cells with RH1-38, it was determined that anti-CD18 antibody inhibited lysis at the effector cell level but not at the target cell level, although CD18 was detectable on the surface of monocyte targets by FACS analysis and immunoprecipitation. Furthermore, specific binding of LAK cells to all targets tested was not affected by the presence of anti-CD18, indicating that lysis of target cells was blocked at a post-binding event. Finally, of the 3 alpha chains associated with CD18, only antibodies to LFA-1 (CD11a) partially blocked binding of LAK cells to monocytes and tumor cells. It is possible, then, that both CD11a and CD18 may work in concert to effect the lysis of target cells by LAK cells.
Blanchard
D K
DK
University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612.
Hall
R E
RE
Djeu
J Y
JY
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology; D018821:CD18 Antigens; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D011233:Precipitin Tests; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion