CD45 mAb induces cell adhesion in peripheral blood mononuclear cells via lymphocyte function-associated antigen-1 (LFA-1) and intercellular cell adhesion molecule 1 (ICAM-1).
A novel cell aggregation-inducing characteristic of the leukocyte common antigen, CD45, is described and its underlying molecular mechanisms investigated. Formation of strong cell clusters was consistently observed in human PBMCs after crosslinking CD45 molecules with antibodies, directed to epitopes common for all CD45 isoforms (e.g., mAb ROS220 or NIH45-2) or the CD45RA (e.g., mAb Alb11) or the CD45RO isoform (e.g., mAb UCHL1). This phenomenon was not seen after PBMC treatment with CD45RA mAb HB11 or CD2 mAb 39C1.5. Identical to phorbol 12-myristate 13-acetate (PMA)-induced clustering, CD45-mediated aggregation was also suppressed by EDTA, by cytochalasin B, and by incubation at 4 degrees C, all characteristics of adhesion mediated by integrins. The involvement of LFA-1 and ICAM-1 in CD45-mediated adhesion was supported by the observation that CD11a (LFA-1 alpha) mAb R7.1, CD18 (LFA-1 beta) mAb R3.3, and CD54 (ICAM-1) mAb R6.1 or RR/l all strongly inhibited CD45- and PMA-induced aggregation. Interestingly, highly pure T lymphocytes did not aggregate in response to CD45 mAb, but did after PMA treatment. These results indicate that triggering human PBMCs via CD45 can cause strong cell aggregation, largely through LFA-1/ICAM-1 interactions. Our findings support an important role of the CD45 antigen in signal transduction and intercellular interaction in human PBMCs.
Lorenz
H M
HM
Department of Internal Medicine III, Institute for Clinical Immunology and Rheumatology, University of Erlangen-Nürnberg, Germany.
Harrer
T
T
Lagoo
A S
AS
Baur
A
A
Eger
G
G
Kalden
J R
JR
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D003080:Cold Temperature; D003571:Cytochalasin B / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007152:Immunologic Capping; D016023:Integrins / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D003571:Cytochalasin B; D004492:Edetic Acid; D017493:Leukocyte Common Antigens