title: Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion through interaction with alpha4beta1 integrin.
abstract: Junctional adhesion molecule-A (JAM-A), JAM-B and JAM-C have been implicated in leucocyte transmigration. As JAM-B binds to very late activation antigen (VLA)-4, a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes to endothelial cells through binding to vascular cell adhesion molecule (VCAM)-1, we hypothesized that JAM-B is also involved in leucocyte rolling and firm adhesion. To test this hypothesis, intravital microscopy of murine skin microvasculature was performed. Rolling interactions of murine leucocytes were significantly affected by blockade of JAM-B [which reduced rolling interactions from 9.1 +/- 2.6% to 3.2 +/- 1.2% (mean +/- standard deviation)]. To identify putative ligands, T lymphocytes were perfused over JAM-B-coated slides in a dynamic flow chamber system. JAM-B-dependent rolling and sticking interactions were observed at low shear stress [0.3 dyn/cm(2): 220 +/- 71 (mean +/- standard deviation) versus 165 +/- 88 rolling (P < 0.001; Mann-Whitney rank sum test) and 2.6 +/- 1.3 versus 1.0 +/- 0.7 sticking cells/mm(2)/min (P = 0.026; Mann-Whitney rank sum test) on JAM-B- compared with baseline], but not at higher shear forces (1.0 dyn/cm(2)). As demonstrated by antibody blocking experiments, JAM-B-mediated rolling and sticking of T lymphocytes was dependent on alpha4 and beta1 integrin, but not JAM-C expression. To investigate whether JAM-B-mediated leucocyte-endothelium interactions are involved in a disease-relevant in vivo model, adoptive transfer experiments in 2,4,-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reactions were performed in mice in the absence or in the presence of a function-blocking JAM-B antibody. In this model, JAM-B blockade during the sensitization phase impaired the generation of the immune response to DNFB, which was assessed as the increase in ear swelling in untreated, DNFB-challenged mice, by close to 40% [P = 0.037; analysis of variance (anova)]. Overall, JAM-B appears to contribute to leucocyte extravasation by facilitating not only transmigration but also rolling and adhesion.
authors.affiliation: Department of Dermatology, Clinic of the J.W. Goethe University, Frankfurt am Main, Germany. ralf.ludwig@uk-sh.de
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.forename: Katja
authors.initials: K
authors.lastname: Hardt
authors.forename: Max
authors.initials: M
authors.lastname: Hatting
authors.forename: Roxana
authors.initials: R
authors.lastname: Bistrian
authors.forename: Sandra
authors.initials: S
authors.lastname: Diehl
authors.forename: Heinfried H
authors.initials: HH
authors.lastname: Radeke
authors.forename: Maurizio
authors.initials: M
authors.lastname: Podda
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Josef M
authors.initials: JM
authors.lastname: Pfeilschifter
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D062765:Junctional Adhesion Molecule B
chemical_list: D015815:Cell Adhesion Molecules; D004139:Dinitrofluorobenzene; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B; C486723:Jam3 protein, mouse