CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3

• DOI: 10.1189/jlb.1006645
• Publication Date: 2008-01-04T01:45:29Z
• Authors: Anja Mueller; Andrea Meiser; Ellen M McDonagh; James M Fox; Sarah J Petit; Georgina Xanthou; Timothy J Williams; James E Pease
• Keywords: CXCR3

Abstract The chemokine CXCL4/platelet factor-4 is released by activated platelets in micromolar concentrations and a chemoattractant for leukocytes via an unidentified receptor. Recently, variant of the human receptor CXCR3 (CXCR3-B) was described, which transduced apoptotic but not chemotactic signals microvascular endothelial cells following exposure to high CXCL4. Here, we show that CXCL4 can induce intracellular calcium release migration T lymphocytes. CXCL4-induced chemotaxis lymphocytes inhibited antagonist pretreatment with pertussis toxin (PTX), suggestive CXCR3-mediated G-protein signaling Gαi-sensitive subunits. Specific binding ligand CXCL10 effectively competed CXCL4, suggesting two are allotopic ligands. We subsequently used expression systems dissect potential roles each isoform mediating function. Transient CXCR3-A CXCR3-B isoforms murine pre-B cell L1.2 produced migrated response manner sensitive PTX antagonist. Binding radiolabeled transfectants low affinity appeared be mediated chiefly glycosaminoglycans (GAGs), as no specific observed GAG-deficient 745-Chinese hamster ovary stably expressing CXCR3. suggest platelet activation, CXCR3/CXCL4 axis may play role lymphocyte recruitment subsequent amplification inflammation diseases such atherosclerosis. In setting, antagonism represent useful, therapeutic intervention.