title: Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.
abstract: Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM.
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Deqing
authors: D
authors: Wu
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Yue
authors: Y
authors: Zeng
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yuting
authors: Y
authors: Fan
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Jianghong
authors: J
authors: Wu
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Tunike
authors: T
authors: Mulatibieke
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Jianbo
authors: J
authors: Ni
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Ge
authors: G
authors: Yu
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Rong
authors: R
authors: Wan
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.|Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xingpeng
authors: X
authors: Wang
authors: Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Guoyong
authors: G
authors: Hu
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007365:Intercellular Junctions / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D010195:Pancreatitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; C486723:Jam3 protein, mouse