title: CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome.
abstract: Hepatopulmonary syndrome (HPS) is a lung complication in various liver diseases, with high incidence, poor prognosis and no effective non-surgical treatments in patients with hepatocirrhosis. Therefore, assessing HPS pathogenesis to explore proper therapy strategies is clinically relevant. In the present study, male Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were set up for 2 weeks of treatment: sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + tumour necrosis factor α (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. Haematoxylin and eosin (H&E) 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 von Willebrand factor (vWf) in CBDL rats. Importantly, CXCR2 inhibition suppressed the activation of Akt and extracellular signal-regulated kinase (ERK) in CBDL rats. Antagonization of TNF-α with PTX down-regulated 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 that enhanced pulmonary angiogenesis by directly acting on the pulmonary tissue. Finally, the present study may provide novel targets for the treatment of HPS.
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi 046000, China qazw3000@126.com.
authors.forename: Xujiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Microbiology, Changzhi Medical College, Changzhi 046000, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi 046000, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Physiology, Changzhi Medical College, Changzhi 046000, China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Liver Disease, Changzhi Medical College, Changzhi 046000, China.
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Changzhi Medical College, Changzhi 046000, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003135:Common Bile Duct / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D020065:Hepatopulmonary Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D010671:Phenylurea Compounds / Q000008:administration & dosage; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D010671:Phenylurea Compounds; D023063:Receptors, Interleukin-8B; C112019:SB 225002; D014409:Tumor Necrosis Factor-alpha
keywords: CXCR2; angiogenesis; hepatopulmonary syndrome