CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stress.
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.
Meissner
Anja
A
Interdisciplinary Center for Clinical Research, Departmen of Experimental Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
Zilles
Olaf
O
Varona
Rosa
R
Jozefowski
Katrin
K
Ritter
Uwe
U
Marquez
Gabriel
G
Hallmann
Rupert
R
Korner
Heinrich
H
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
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