title: Activation of CD44 induces ICAM-1/LFA-1-independent, Ca2+, Mg(2+)-independent adhesion pathway in lymphocyte-endothelial cell interaction.
abstract: We have established an endothelial cell line KOP2.16 from pooled mouse lymph nodes. Resting lymphocytes avidly bound to KOP2.16 and migrated underneath the cytoplasm. The binding was partly mediated by VLA-4 and VCAM-1, but apparently independent of CD44 since anti-CD44 antibody examined failed to inhibit the binding. However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca(2+)-, Mg(2+)-independent, LFA-1/ICAM-1-, CD2/LFA-3, VLA-4/VCAM-1-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment. Interestingly, the elicited adhesion was observed only when anti-CD44 that block hyaluronate recognition of CD44 were used for lymphocyte pretreatment. Neither hyaluronate itself nor non-blocking anti-CD44 up-regulated the adhesion. Fab fragment of the blocking anti-CD44 did not induce the up-regulation unless cross-linked with a second antibody, indicating that cross-linking of surface CD44 is necessary for induction of a novel adhesion pathway. We propose that the agonistic anti-CD44 antibodies induce a novel adhesion pathway by mimicking ligand binding to CD44 on the lymphocyte surface and that non-hyaluronate ligand(s) is involved in regulation of adhesive function of CD44. Potential involvement of such a regulatory mechanism in lymphocyte homing is discussed.
authors.affiliation: Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Toyama-Sorimachi
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008274:Magnesium / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D016029:Receptors, Very Late Antigen / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium; D002118:Calcium