title: CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stress.
abstract: Chemokines are thought to control lymphocyte recruitment to the inflamed endothelium. To dissect chemokine-mediated adhesion, binding of ex vivo isolated splenocytes to tumor necrosis factor (TNF)-activated endothelial cells was analyzed under shear stress. We observed specific adhesion of naive follicular B cells, which could be blocked by pertussis toxin. This indicated a G protein-mediated binding and pointed at a contribution of chemokine receptors to B-cell adhesion. Analysis of chemokines expressed by TNF-activated endothelial cells showed that CC chemokine ligand 2 (CCL2), CCL17, and CCL20 were up-regulated. Only on follicular B cells was the cognate receptor for CCL20, CC chemokine receptor 6 (CCR6), expressed strongly, and a functional transmigration assay with CCR6-negative B cells demonstrated conclusively the sole signaling of CCL20 through CCR6. Desensitization of CCR6 on naive B cells with CCL20 resulted in receptor down-regulation and reduced B-cell adhesion. We conclude that CCL20 plays a vital role in B-cell adhesion to the inflamed endothelium.
authors.affiliation: Interdisciplinary Center for Clinical Research, Departmen of Experimental Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Meissner
authors.forename: Olaf
authors.initials: O
authors.lastname: Zilles
authors.forename: Rosa
authors.initials: R
authors.lastname: Varona
authors.forename: Katrin
authors.initials: K
authors.lastname: Jozefowski
authors.forename: Uwe
authors.initials: U
authors.lastname: Ritter
authors.forename: Gabriel
authors.initials: G
authors.lastname: Marquez
authors.forename: Rupert
authors.initials: R
authors.lastname: Hallmann
authors.forename: Heinrich
authors.initials: H
authors.lastname: Korner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D054418:Chemokine CCL20; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D007249:Inflammation; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins