Selective human endothelial cell activation by chemokines as a guide to cell homing.
An original model of organo-specific, immortalized and stabilized endothelial cell lines was used to delineate the part played by some chemokines (CCL21, CX3CL1, CCL5 and CXCL12) and their receptors in endothelium organo-specificity. Chemokine receptor expression and chemokine presentation were investigated on organo-specific human endothelial cell lines. Although the chemokines showed distinct binding patterns for the various endothelial cell lines, these were not correlated with the expression of the corresponding receptors (CX3CR1, CXCR4, CCR5 and CCR7). Experiments with CCL21 on peripheral lymph node endothelial cells demonstrated that the chemokine did not co-localize with its receptor but was associated with extracellular matrix components. The specific activity of chemokines was clearly shown to be related to the endothelial cell origin. Indeed, CX3CL1 and CCL21 promoted lymphocyte recruitment by endothelial cells from the appendix and peripheral lymph nodes, respectively, while CX3CL1 pro-angiogenic activity was restricted to endothelial cells from the appendix and skin. The high specificity of the chemokine/endothelium interaction allowed the design of a direct in vitro endothelial cell targeting assay. This unique cellular model demonstrated a fundamental role for chemokines in conferring on the endothelium its organo-specificity and its potential for tissue targeting through the selective binding, presentation and activation properties of chemokines.
Crola Da Silva
Claire
C
Center for Molecular Biophysics, UPR CNRS affiliated to Orléans University and INSERM, Rue Charles Sadron, France.
Lamerant-Fayel
Nathalie
N
Paprocka
Maria
M
Mitterrand
Michèle
M
Gosset
David
D
Dus
Danuta
D
Kieda
Claudine
C
D043925:Angiogenesis Inducing Agents / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; C515478:CCL21 protein, human; C515538:CX3CL1 protein, human; D054421:Chemokine CCL21; D054428:Chemokine CX3CL1; D018925:Chemokines; D019707:Receptors, Chemokine
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