An ex vivo model to study the monocyte-endothelial cell interaction in the prelesional stage of experimentally-induced atherogenesis in hamster.
We imagined an ex vivo atherogenic model consisting in hypercholesterolemic versus normocholesterolemic aortic arch rings or sigmoid valves incubated in cell culture conditions with human monocytes. Normal tissues did not show any attached monocytes. On the atherogenic aortic arch three different aspects were observed: a) there were no monocytes attached on a normal zone; b) many monocytes adhered to the endothelium on a thickened area, with intimal smooth muscle cells infiltration, and c) the greatest number of attached monocytes was seen in mechanically injured zones of the aortic arch, where the subendothelial area was totally exposed. Immunohisto- and immunocytochemistry for LFA-1 revealed the presence of this leukocyte integrin on monocyte plasma membrane. The labelled monocyte had an activated shape, with pseudopodes extended over the endothelial cells and the anti-LFA-1 antibody coupled with colloidal gold decorating areas apposing to a morphologically modified endothelium. In conclusion, the ex vivo model reproduced the in vivo situations where the monocytes adhere to the modified endothelium covering the thickened areas of hypercholesterolemic aortic wall; they express at least one of the adhesion integrins, namely LFA-1. This study intended to contribute, at least in part, to the understanding of some mechanisms governing the monocyte-endothelial cell interactions in hypercholesterolemia.
Constantinescu
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E
Institute of Cell Biology and Pathology Nicolae Simionescu, Bucharest, Romania. econstantinescu@simionescu.instcellbiopath.ro
Alexandru
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D
Alexandru
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V
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002791:Cholesterol, Dietary / Q000009:adverse effects; D006224:Cricetinae; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000378:metabolism / Q000648:ultrastructure*; D009924:Organ Culture Techniques
D002791:Cholesterol, Dietary; D016169:Lymphocyte Function-Associated Antigen-1