The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection

Abstract

CXCR7 is an atypical receptor for the chemokines CXCL11 and CXCL12, which were found to be involved in animal models of allograft injury. We studied the expression of CXCR7 and its ligands in human kidneys by first quantifying the mRNA in 53 renal allograft biopsies. Receptor and ligand mRNAs were expressed in renal allografts, with a significant induction of CXCL11 and CXCL12 in biopsies showing borderline lesions and acute rejection. Immunohistochemical analysis for CXCR7 was performed in a series of 64 indication and 24 protocol biopsies. The indication biopsies included 46 acute rejections, 6 with interstitial fibrosis and tubular atrophy, and 12 pretransplant biopsies as controls. In control biopsies, CXCR7 protein was found on smooth muscle and on endothelial cells of a small number of peritubular vessels. The number of CXCR7-positive vessels was increased in acute rejection and, using double immunofluorescence labeling, a subset of these CXCR7-positive endothelial cells were identified as lymphatic vessels. Both CXCR7-positive blood and lymphatic vessels increased during allograft rejection. We found that CXCR7 is present in both blood and lymphatic endothelial cells in human renal allografts. Whether its presence modulates the formation of chemokine gradients and the recruitment of inflammatory cells will require further experimental studies.

A role for the CXCL12 receptor, CXCR7, in the pathogenesis of human pulmonary vascular disease

“…In humans, CXCR7 was previously reported not to be expressed in endothelium of normal systemic organs in vivo but highly expressed in tumour-associated vasculature or in endothelial cells during human renal allograft rejection [21,22]. We now show that, contrary to the vasculature of systemic organs, CXCR7 is present on the pulmonary endothelium under normal circumstances in vivo.…”

Antagonism of CXCR7 attenuates chronic hypoxia–induced pulmonary hypertension

“…Although expression patterns for this receptor remain controversial (8,9,13,25,26), there is general agreement that it can be expressed on the membranes of endothelial cells and smooth muscle cells in various tissues (9,16,20,27). The ligands for CXCR7 are CXCL11 and SDF-1 (ref.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…The chemokines currently encompass over 50 cytokines and 20 receptors. Many chemokines and chemokine receptors are prominently upregulated in renal transplants with renal fibrosis (313)(314)(315)(316). The CC-motif chemokine 2 (CCL2) and its receptor CCR2 are closest to being targeted in human renal fibrosis.…”