Lipopolysaccharide directly affects pancreatic acinar cells - Implicationson acute pancreatitis pathophysiology

We have explored whether lypopolisaccharide (LPS, endotoxin) induces pancre atic injury on pancreatic acinar cells both in vivo and in vitro. Wistar ma le rats were treated with four intraperitoneal injections of 10 mg/kg LPS, and AR4-2J cells were exposed to increasing doses of LPS. Expression of pan creatitis-associated-protein (PAP) mRNA was strongly induced in AR4-2J cell s exposed to LPS, while amylase mRNA was reduced. LPS also induced apoptosi s and expression of TNF-alpha, IL-1 beta, and IL-8 mRNA in AR4-2J cells. Th e in vivo effect of LPS showed structural signs of cellular damage, includi ng numerous cytoplasmic vacuoles. severe nuclear alterations, and high expr ession of PAP mRNA. This study demonstrated that LPS induced pancreatic dam age by directly affecting the pancreatic acinar cells. The role of LPS in t he pathophysiology of acute pancreatitis may be partly due to the effect LP S has on the acinar cell.