Animal models to study the role of pulmonary intravascular macrophages in spontaneous and induced acute pancreatitis.

Abstract

Acute necrotizing pancreatitis (ANP) is a common gastrointestinal cause of emergency admissions in dogs and humans and can lead to a systemic inflammatory response syndrome resulting in multiple organ dysfunction syndrome. Among the various complications associated with ANP, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a major contributor leading to high mortality rates associated with severe acute pancreatitis (AP) in human patients. The incidence of ALI/ARDS in ANP dogs is not well-characterized in spontaneous AP and there are no models to study it in rodent models. Most of the data related to AP comes from rodent models of AP, which may not always represent the true mechanisms occurring in the lungs of dogs or humans with ANP. Therefore, this manuscript provides a review of current and potential models to study the role of pulmonary intravascular macrophages (PIMs) in acute pancreatitis. Recently, we characterized lung inflammation in clinical cases of AP in dogs and found significant recruitment of PIMs which have been credited as pro-inflammatory cells in species such as cattle, horse, pigs, and sheep that normally have them. Considering the pro-inflammatory roles of constitutive or induced PIMs, we investigated whether a well-established mouse model of ANP has induced PIMs. We found induced PIMs in L-arginine-induced ANP in mouse and that MCP-1 is important in PIM induction in this model. Taken together, now we summarize information on spontaneous ANP in dog and a mouse model of induced ANP to study mechanisms of lung dysfunction and the role of PIMs during ANP.