title: Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affinity very late antigen-4.
abstract: It has been shown that cells with high affinity very late Ag (VLA)-integrins have up-regulated expression of a beta1-subunit epitope, which is detected by 15/7 mAb. In this study, we demonstrate that soluble VCAM-1 (sVCAM-1) exhibits chemotactic activity of T cells with high affinity VLA-4 against VCAM-1, such as Jurkat T cells and IL-2-dependent T cells. Moreover, we found that T cells in the synovial fluid show high basal migration in the absence of sVCAM-1, compared with peripheral blood T cells in patients with rheumatoid arthritis. Among T cells in the synovial fluid, CD45RO+ memory T cells, in response to sVCAM-1, showed a much higher than basal migratory response when compared with CD45RA+ naive cells, while no significant difference was observed between CD4+ and CD8+ T cells. The chemotactic activity of sVCAM-1 is inhibited in the presence of anti-VCAM-1 and anti-VLA-4, which interfered with the binding between VCAM-1 and VLA-4. Inhibition studies using various kinase inhibitors (C3 exoenzyme, KN62, and H7) show that Rho, Ca2+/calmodulin-dependent kinase II, and protein kinase C are involved in signal transduction in sVCAM-1-induced chemotaxis, respectively, whereas tyrosine kinase seems to play a lesser role, since genistein showed only partial inhibition of T cell chemotaxis. Western blot analysis using an anti-phospho-serine mAb (MO82) reveals that Ser82 in the vimentin is phosphorylated specifically by Ca2+/calmodulin-dependent kinase II through sVCAM-1 activation in the IL-2 dependent T cells. Collectively, by inducing migration and recruitment of T cells through several kinase activations, sVCAM-1 contributes to the development of the inflammation of synovial lesion.
authors.affiliation: Department of Immunology, School of Medicine, Kagoshima University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kitani
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: T
authors.initials: T
authors.lastname: Izumihara
authors.forename: M
authors.initials: M
authors.lastname: Inagaki
authors.forename: X
authors.initials: X
authors.lastname: Baoui
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Matsuyama
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017635:Clonal Anergy; D004789:Enzyme Activation; D006801:Humans; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000096:biosynthesis / Q000235:genetics; D016023:Integrins / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D019169:Jurkat Cells / Q000187:drug effects*; D015458:Leukemia, T-Cell / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology
chemical_list: D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017493:Leukocyte Common Antigens