Role of macrophage overactivation in the development of acute pancreatic injury in rats.
BACKGROUND
An increase in systemic inflammatory mediators from stimulated leucocytes and macrophages has been noted during acute pancreatitis. The role of cytolytic inflammatory macrophages and potential mechanisms in the development of acute pancreatic injury and endothelial barrier dysfunction are less well defined.


METHODS
Rats were challenged by an intraperitoneal injection of cytolytic or non-cytolytic inflammatory macrophage stimulators at various concentrations. The effects of oxygen free radicals, prostaglandin and extracellular calcium influx on macrophage-associated pancreatic endothelial compromise, measured by pancreatic intravascular plasma volume, pancreatic interstitial fluid volume, and the pancreatic extravascular human serum albumin distribution volume, were explored.


RESULTS
Zymosan-induced overactivation of cytolytic inflammatory macrophages resulted in the development of acute pancreatic endothelial dysfunction in a dose- and time-dependent pattern. An increase in pancreatic water content and interstitial fluid volume was observed following a higher dose (0.5 mg/g) of concanavalin A without alteration in plasma lipase level, while thioglycollate medium did not compromise pancreatic endothelial barrier function. Oxygen free radicals, but also prostaglandins and extracellular calcium influx, seemed to be involved in macrophage overactivation-induced pancreatic injury.


CONCLUSIONS
Overactivation of cytolytic macrophages plays a role in the pathogenesis of pancreatic injury by initiating the development of endothelial barrier dysfunction. Multiple inflammatory mediators from overactivated macrophages act as intercellular signals between macrophages and the endothelium during acute pancreatic injury.
Andersson
R
R
Department of Surgery, Lund University Hospital, Sweden.
Deng
X M
XM
Wang
X D
XD
D000818:Animals; D001834:Body Water / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D004727:Endothelium; D005110:Extracellular Space; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013864:Thioglycolates / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D013864:Thioglycolates; D003208:Concanavalin A; D015054:Zymosan