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

作者：Costello Christine M^*; McCullagh Brian; Howell Katherine; Sands Michelle; Belperio John A; Keane Michael P; Gaine Sean; McLoughlin Paul

来源：European Respiratory Journal, 2012, 39(6): 1415-1424.

DOI：10.1183/09031936.00044911

• CXCR7
• CXCR4
• CXCL12
• hypoxia
• pulmonary vasculature

Given the critical role that endothelial cell dysfunction plays in the pathogenesis of pulmonary hypertensive diseases, we set out to establish if CXCR7, a receptor for the proangiogenic ligand CXCL12, is expressed in the vasculature of human lung diseases and examine its role in mediating CXCL12-induced responses in primary pulmonary human microvascular endothelial cells. %26lt;br%26gt;Receptor and ligand expression was examined in control and explanted human hypertensive lungs, in human plasma and in hypoxic rodent lungs, by ELISA and immunohistochemical studies. Functional in vitro experiments examined the role of CXCR7 in CXCL12-induced lung microvascular endothelial cell proliferation, migration, and wound regeneration and repair. %26lt;br%26gt;CXCR7 is elevated in the endothelium of explanted human hypertensive lungs and circulating CXCL12 concentrations are significantly elevated in disease. We demonstrate that alveolar hypoxia similar to that found in lung disease increases CXCR7 expression in the pulmonary endothelium. Furthermore, CXCR7 is the receptor through which endothelial cell regeneration and repair, and proliferation, is mediated, whereas signalling via CXCR4 is essential for chemotactic cell migration. %26lt;br%26gt;Our findings demonstrate that CXCR7 has a critical but previously unrecognised role to play in endothelial cell proliferation, suggesting that CXCR7-mediated signalling may be functionally important in pulmonary vascular diseases.

• 出版日期2012-6