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Ischemia/reperfusion-induced granulocyte influx is a multistep process mediated by mast cells
1Immunological Sciences Research Group, University of Calgary Medical Center, Alberta, Canada.
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.
Conclusion:
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.
Insights
Mast cells significantly contribute to polymorphonuclear leukocyte (PMN) recruitment during reperfusion of postischemic tissues. Cromolyn, an antiallergy agent, reduced PMN rolling, adhesion, and emigration, suggesting therapeutic potential.
Area of Science:
- Gastroenterology
- Immunology
- Vascular Biology
Background:
- Polymorphonuclear leukocyte (PMN) recruitment to postischemic tissues involves rolling, reduced velocity, adhesion, and emigration.
- Mast cells are implicated in inflammatory processes, but their role in reperfusion-induced PMN recruitment is not fully understood.
Purpose of the Study:
- To investigate the role of mast cells in reperfusion-induced PMN recruitment.
- To assess the effect of mast cell stabilization on PMN rolling, adhesion, and emigration.
Main Methods:
- Intravital microscopy was used to visualize cat small intestinal venules.
- Animals underwent 60 minutes of ischemia followed by 60 minutes of reperfusion.
- Cromolyn, a mast cell stabilizer, was administered to pretreated animals.
Main Results:
- Reperfusion significantly increased PMN rolling, adhesion, and emigration in untreated animals.
- Cromolyn pretreatment initially increased PMN rolling but significantly reduced it by 10 minutes.
- Cromolyn also reduced PMN adhesion and emigration throughout the reperfusion period.
Conclusions:
- Interstitial mast cells play a significant role in the multistep recruitment of PMNs to postischemic tissues.
- Antiallergy agents like cromolyn may offer a therapeutic strategy for managing postischemic conditions in the intestine.