CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome

In this study, male Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were setup for 2 weeks of treatment: Sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + TNF-α antagonist PTX, and CBDL + normal saline groups. Liver and lung tissues were collected after mean arterial pressure (MAP) and portal venous pressure (PVP) measurements. Hematoxylin and Eosin staining (lung) and Masson staining (liver) were performed for pathological analyses. Finally, pulmonary tissue RNA and total protein were assessed for target effectors. The mRNA and protein levels of CXCR2 were significantly increased in the pulmonary tissue of CBDL rats. What's more, CXCR2 inhibition by SB225002 reduced the expression of CD68 and vWf in CBDL rats. Importantly, CXCR2 inhibition suppressed the activation of Akt and ERK in CBDL rats. Antagonization of TNF-α with PTX downregulated the expression of CXCR2. During HPS pathogenesis in rats, CXCR2 might be involved in the accumulation of pulmonary intravascular macrophages and angiogenesis, possibly by activating Akt and ERK, with additional regulation by TNF-α which enhanced pulmonary angiogenesis by directly acting on the pulmonary tissue. Finally, this study may provide novel targets for the treatment of HPS.

Source: Clinical Science - November 21, 2016 Category: Biomedical Science Authors: li, X., Chen, Y., Chang, Y., LI, S., Zhao, Z., Zhang, H. Tags: PublishAheadOfPrint Source Type: research