Leukocyte recruitment to atherosclerotic lesions.
Atherosclerosis is a complex disease process in which monocytes and lymphocytes are recruited from the blood into the arterial intima. Mouse models of atherosclerosis have been developed, carefully characterized and used to elucidate molecular mechanisms of atherosclerotic lesion formation. Deficiency of various chemokines, chemokine receptors and leukocyte adhesion molecules that are known to participate in mononuclear leukocyte emigration, such as monocyte chemoattractant protein-1 and its receptor chemokine (CC motif) receptor 2, CX3C chemokine receptor 1 and vascular cell adhesion molecule 1, results in decreased formation of atherosclerotic lesions. In these studies, analysis was usually limited to assessment of lesion size, cellular composition and histological features. An assumption is often made that leukocyte recruitment is diminished if a reduction in lesions is found in chemokine- or adhesion molecule-deficient animals. However, direct quantification of leukocyte recruitment to atherosclerotic lesions is lacking and there is a need for practical recruitment assays that have the potential to provide precise and novel insights. For example, insights may be gained to distinguish the contribution of chemokines, chemokine receptors and adhesion molecules to the recruitment, survival or proliferation of different leukocyte types in atherosclerotic lesions.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto General Research Institute, University Health Network, Toronto, Canada. myron.cybulsky@utoronto.ca
Myron I
MI
Cybulsky
Doyon
D
Won
Mehran
M
Haidari
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D011897:Random Allocation; D019707:Receptors, Chemokine / Q000378:metabolism; D012680:Sensitivity and Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D020523:Chemokines, CX3C; D019007:P-Selectin; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1