Ischemia/reperfusion-induced granulocyte influx is a multistep process mediated by mast cells.
OBJECTIVE
The influx of polymorphonuclear leukocytes (PMNs) that occurs at the onset of reperfusion of postischemic tissue is a multistep mechanism that includes initial rolling of PMNs, a progressive reduction in PMN rolling velocity, and ultimately PMN adhesion and emigration. In this study we assessed whether mast cells play a role in reperfusion-induced PMN recruitment with emphasis on PMN rolling, adhesion, and emigration.


METHODS
Cat small intestinal venules were visualized using intravital microscopy during control, 60 min of ischemia (intestinal blood flow 20% of control), and 60 min of reperfusion in untreated and cromolyn- (mast cell stabilizer) pretreated animals.


RESULTS
Between 1 and 5 min of reperfusion, there was a very dramatic rise in PMN rolling which persisted for the next 60 min. In cromolyn-pretreated animals, the flux of rolling PMNs increased in the very early (5 min) reperfusion period, but by 10 min the number of rolling leukocytes was significantly reduced, an event that persisted for the next 60 min. PMNs rolled at a velocity of 40% of control values for the first 10 min of reperfusion without a change in hemodynamic values but returned toward control values by 60 min of reperfusion. An identical velocity profile was observed for the cromolyn-treated animals. In untreated animals, PMN adhesion and emigration was significantly increased throughout the reperfusion period, whereas the cromolyn-pretreated animals had reduced adhesion (60 min of reperfusion) and a reduced rate of emigration throughout the reperfusion period.


CONCLUSIONS
Interstitial mast cells contribute significantly to the multistep recruitment (rolling, adhesion, and emigration) of PMNs from blood to postischemic tissues and raise the possibility that antiallergy agents such as cromolyn may be a useful form of therapy in the postischemic intestine.
Kanwar
S
S
Immunological Sciences Research Group, University of Calgary Medical Center, Alberta, Canada.
Kubes
P
P
D000818:Animals; D001794:Blood Pressure; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology; D006098:Granulocytes / Q000378:metabolism*; D007421:Intestine, Small / Q000098:blood supply; D007511:Ischemia / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000473:pathology*
D004205:Cromolyn Sodium