Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction.
BACKGROUND
Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP).


METHODS
AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured.


RESULTS
The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0.05), decreased the release of histamine at 1 h (P < 0.05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0.05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation.


CONCLUSIONS
Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction.
Dib
M
M
Department of Surgery, Lund University Hospital, Sweden.
Zhao
X
X
Wang
X D
XD
Andersson
R
R
D000208:Acute Disease; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D006632:Histamine / Q000032:analysis; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D009102:Multiple Organ Failure / Q000209:etiology* / Q000473:pathology; D010179:Pancreas / Q000098:blood supply; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013657:Taurodeoxycholic Acid / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018932:Chemokine CCL2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D013657:Taurodeoxycholic Acid; D006632:Histamine; D009195:Peroxidase