Ligation of CD53/OX44, a tetraspan antigen, induces homotypic adhesion mediated by specific cell-cell interactions.
The CD53 antigen is a member of the tetraspan family of proteins with unknown function. Stimulation of rat IR938F B-cell lymphoma cells with monoclonal antibody MRC OX44 (anti-rat CD53) triggered a homotypic adhesion reaction which reached a maximum effect at 24 hr. This effect occurred at 37 degrees C but not at 4 degrees C. Adhesion was prevented by removal of divalent cations, Ca2+ and Mg2+, with EGTA and EDTA as chelating agents. The adhesion induced by MRC OX44 was inhibited by cycloheximide and actinomycin D, suggesting that de novo protein synthesis was required for this effect. The addition of mAb WT1 against rat LFA-1 (CD11a) antigen had no effect on adhesion, suggesting that the cell-cell interaction is not mediated by the expression of LFA-1 antigen. The intracellular signals required to induce adhesion were inhibited by two tyrosine kinase inhibitors, genistein and piceatannol. Wortmannin, a selective inhibitor of phosphoinositide 3-kinase activity, completely blocked adhesion. Two protein kinase C inhibitors, H7 and bisindolylmaleimide, inhibited the adhesion, suggesting that part of the signal is mediated by PKC. Electron microscopy of aggregated cells showed that the interaction is localized to short membrane regions, where contact areas of higher density in opposing zones from both cells were detected. We postulate that there is a common adhesion mechanism that is modulated by several tetraspan family members and associated proteins. This adhesion structure might represent a novel form of cell communication among lymphoid cells.
Lazo
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Unidad de Genética y Medicina Molecular (Consejo Superior de Investigaciones Científicas), Instituto de Salud Carlos III, Majadahonda, Spain. plazozbi@isciii.es
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Gutierrez del Arroyo
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D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology*; D002413:Cations, Divalent; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002450:Cell Communication; D003571:Cytochalasin B / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016393:Lymphoma, B-Cell / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D019000:Phosphotyrosine / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D060265:Tetraspanin 25; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C554894:CD53 protein, human; D002413:Cations, Divalent; C554896:Cd53 protein, rat; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D060265:Tetraspanin 25; D014415:Tunicamycin; D019000:Phosphotyrosine; D003571:Cytochalasin B; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C