Ischemia/reperfusion induces the recruitment of leukocytes from whole blood under flow conditions.
Ischemia/reperfusion (I/R) occurs in a number of pathological conditions, including myocardial infarction, stroke, and organ transplantation. During the reperfusion phase, leukocytes are recruited into affected tissues, where they can cause tissue damage and organ failure. Various in vitro models have been developed to study the role of adhesion molecules in I/R-mediated leukocyte recruitment. These models traditionally use isolated leukocytes and static conditions and, therefore, may not recapitulate the in vivo situation. We developed two novel in vitro models of I/R-mediated leukocyte recruitment in which leukocyte recruitment was examined using whole blood under shear conditions. Chemical treatments were used to mimic I/R in the first model, while sequential exposure to hypoxia/reoxygenation (H/R) was used to mimic I/R in the second model. We found that leukocytes were recruited from whole blood under shear conditions to endothelial cells treated with chemically induced I/R or H/R. In both models, mRNA for intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin was upregulated. The role of adhesion molecules in leukocyte recruitment differed slightly between the two models, with E-selectin and VCAM-1 playing approximately equal roles in leukocyte recruitment in the chemically induced I/R model and VCAM-1 being a central mediator of leukocyte recruitment in the H/R model.
Cassie
Scott
S
Department of Medicine, Immunology Research Group, University of Calgary, Calgary, Alberta, Canada.
Masterson
Mark F
MF
Polukoshko
Andrew
A
Viskovic
Mirjana Maric
MM
Tibbles
Lee Anne
LA
D001773:Blood Cells / Q000502:physiology; D003847:Deoxyglucose / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036904:Leukocyte Rolling / Q000502:physiology*; D015427:Reperfusion Injury / Q000139:chemically induced / Q000503:physiopathology*; D019810:Sodium Azide / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019810:Sodium Azide; D003847:Deoxyglucose