title: Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response.
abstract: Plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). Endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133+and VEGFR-2+cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. Broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using gene-modified inflammation-resistant EPCs.
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Fan-Guo
authors.initials: FG
authors.lastname: Juan
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ali Q
authors.initials: AQ
authors.lastname: Shah
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002645:Chickens; D018920:Coculture Techniques; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007107:Immune System; D007150:Immunohistochemistry; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D011651:Pulmonary Artery / Q000503:physiopathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D017228:Hepatocyte Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Plexiform lesions; Endothelial progenitor cells; Immune response; Hepatocyte growth factor; Broiler chicken