Mast cells contribute to ischemia-reperfusion-induced granulocyte infiltration and intestinal dysfunction.
The objective of this study was to determine whether ischemia-reperfusion (I/R) of the small bowel activated mast cells and, if so, to determine whether this event contributed to granulocyte infiltration and mucosal barrier dysfunction. Autoperfused segments of the jejunum were exposed to 30 min of ischemia followed by 60 min of reperfusion. Epithelial permeability was assessed by the clearance of 51Cr-labeled EDTA from plasma to lumen. Plasma rat mast cell protease II (RMCP II) was measured and used as an index of mucosal mast cell degranulation, whereas myeloperoxidase (MPO) activity was used as an index of granulocyte infiltration. I/R caused a significant increase in plasma RMCP II levels, MPO activity, and epithelial permeability. The mucosal mast cell stabilizer doxantrazole prevented the I/R-induced increase in all three parameters. The connective tissue mast cell stabilizer ketotifen had no effect. To determine whether oxidants were involved in mast cell degranulation, some animals were pretreated with superoxide dismutase and catalase. This regimen completely abolished the I/R-induced rise in plasma RMCP II levels and attenuated mucosal MPO activity and epithelial permeability. Selective inhibitors of two mast cell-derived mediators, platelet-activating factor and histamine, did not attenuate the rise in epithelial permeability. These data suggest that oxidant-induced mucosal mast cell degranulation is a key event in the granulocyte infiltration and tissue dysfunction associated with reperfusion of the ischemic intestine.
Kanwar
S
S
Department of Medical Physiology, University of Calgary, Canada.
Kubes
P
P
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002465:Cell Movement; D006098:Granulocytes / Q000502:physiology*; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008666:Metalloendopeptidases / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus