Bimolecular complex between rolling and firm adhesion receptors required for cell arrest; CD44 association with VLA-4 in T cell extravasation.
CD44 on activated T cells can initiate contact and mediate rolling on hyaluronan on endothelial cells. We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction with this rolling interaction for firm adhesion. Here, we show by coimmunoprecipitation and transfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cells. Absence of the cytoplasmic portion of CD44 abrogates this coassociation and attendant firm adhesion. Moreover, in an in vivo model of lymphocyte homing, cells expressing only the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defining a discrete biological role for the cytoplasmic domain. These studies demonstrate a molecular mechanism whereby coanchoring within a single bimolecular complex between a primary and secondary adhesion molecule regulates a cell's ability to firmly adhere, providing a fundamental alteration to the paradigm of leukocyte extravasation.
Nandi
Animesh
A
Laboratory of Molecular Pathology, Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Estess
Pila
P
Siegelman
Mark
M
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D015638:Cytochalasin D / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D036904:Leukocyte Rolling / Q000187:drug effects / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011233:Precipitin Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D018960:Hyaluronan Receptors; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D