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Mouse Model to Study Pulmonary Intravascular Macrophage Recruitment and Lung Inflammation in Acute Necrotizing Pancreatitis

Mouse Model to Study Pulmonary Intravascular Macrophage Recruitment and Lung Inflammation in Acute Necrotizing Pancreatitis

Vanessa Vrolyk, David Schneberger, Khanh Le, Bruce K Wobeser, Baljit Singh

Cell Tissue Res. 2019 Oct;378(1):97-111.

PMID: 31037357

Abstract:

Patients suffering from severe acute pancreatitis (AP) can develop acute lung injury (ALI) with poor outcomes and the mechanisms involved remain incompletely understood. Pulmonary intravascular macrophages (PIMs), which are credited as promoters of ALI, are not constitutively present in humans and rodents; however, there is evidence of PIM recruitment in rodents during some pathological conditions, such as hepatic diseases. Therefore, this study assesses PIM recruitment in the lungs of a mouse model of acute necrotizing pancreatitis (ANP) induced with L-arginine monohydrochloride. Mice were euthanized after 24 h, 72 h and 120 h. Control mice received sham injections of saline. Pancreatic histopathological grading and plasma amylase were used to confirm the development of ANP in L-arginine-treated mice. Histopathological grading of lungs from the ANP mice at 72 h showed increased mononuclear phagocytes in alveolar septa, compared to that from the controls. Lungs from the ANP mice also showed increased numbers of CD68-immunopositive alveolar septal macrophages, suggestive of PIM recruitment, compared to those from the controls. Lungs from the ANP mice showed increased expression of IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and von Willebrand factor compared to those from the controls. The recruitment of CD68-positive septal macrophages was not observed in MCP-1 knockout mice with ANP at 72 h when compared to C57BL/6 wild-type mice. Taken together, we developed a mouse model of PIM recruitment dependent on MCP-1 that allows us to explore their roles in ANP-associated ALI.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1119342-A	L-Arginine monohydrochloride		1119-34-2	Price

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