LFA-1-mediated leukocyte adhesion regulated by interaction of CD43 with LFA-1 and CD147.
The activity of the lymphocyte-function associated antigen 1 (LFA-1; CD11a/CD18) must be tightly controlled during the onset of cellular immunity. It is well known that the sialoglycoprotein CD43 can influence LFA-1-mediated cell adhesion in an either anti- or pro-adhesive manner through mechanisms not well understood. By using a yeast-2-hybrid screen and co-immunoprecipitation we identified physical association of CD43 with two novel partners, LFA-1 itself and the Ig-family member CD147 (EMMPRIN, basigin), and characterized how these interactions are involved in LFA-1-mediated cell adhesion. Monoclonal antibodies (mAbs) to both CD43 and CD147 induced similar homotypic cell aggregation and adhesion of Jurkat T cells and U937 myeloid cells. Both CD43 and CD147 mAbs induced dynamic co-capping of LFA-1 together with the CD43 and the CD147 molecule to cell contact zones. However, in contrast to CD43, we were not able to co-immunoprecipitate LFA-1 with CD147, which indicates that CD43 interacts with CD147 and LFA-1 in two distinct but similarly reorganized complexes. Co-transfection of CD43 interfered with the CD147-induced cell adhesion and aggregation, and siRNA-mediated knock down of CD43 in human T cells resulted in enhanced LFA-1 activation induced via CD147 and also the T cell antigen receptor. These results indicate that triggering CD43 and the underlying signaling pathways enhance LFA-1 adhesiveness while CD43 also negatively regulates LFA-1 induction via other receptors by dynamic interaction with either LFA-1 or CD147.
Khunkaewla
Panida
P
Department of Molecular Immunology, Center for Physiology, Pathophysiology & Immunology, Medical University of Vienna, Vienna, Austria.
Schiller
Herbert B
HB
Paster
Wolfgang
W
Leksa
Vladimír
V
Cermák
Lukás
L
Andera
Ladislav
L
Horejsí
Václav
V
Stockinger
Hannes
H
D000818:Animals; D051926:Basigin / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D051917:Leukosialin / Q000235:genetics / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D011485:Protein Binding
C497886:BSG protein, human; D051917:Leukosialin; D016169:Lymphocyte Function-Associated Antigen-1; C465014:SPN protein, human; D051926:Basigin