Mast cells contribute to early pancreatitis-induced systemic endothelial barrier dysfunction.
BACKGROUND
Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiological process of acute conditions. The aim of the study was to evaluate the effect of mast cell stimulation on the early development of multiple organ dysfunction (MODS) in acute pancreatitis (AP).


METHODS
AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Tissue endothelial barrier dysfunction (TEBD) was measured by plasma exudation of radiolabeled albumin. Activation of mast cells was estimated by measuring the release of histamine. Mast cell stimulation was achieved with compound 48/80 (C48/80) administered intravenously (i.v.) or intraperitoneally (i.p.) in different doses either as pretreatment (30 min prior to induction of AP) or treatment immediately after induction of AP.


RESULTS
Administration of C48/80 both i.p. and i.v. demonstrated the same effects. A single pretreatment dose of C48/80 (0.5 mg/kg) significantly reduced AP-induced TEBD in the pancreas and gut. Administration of C48/80 immediately after sham operation or induction of AP resulted in a significant increase in pancreatic and intestinal TEBD (p < 0.05 vs. AP+saline). Plasma levels of histamine increased with increasing doses of C48/80.


CONCLUSIONS
The results imply that mast cell activation could be involved in the initiation of AP and the early phase of AP-induced MODS. Mechanisms seem to be complex and are still to be elucidated.
Department of Surgery, Lund University Hospital, Lund, Sweden.
Marwan
M
Dib
Xia
X
Zhao
Xiangdong
X
Wang
Roland
R
Andersson
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009102:Multiple Organ Failure / Q000209:etiology; D010195:Pancreatitis / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003189:p-Methoxy-N-methylphenethylamine