Influence of anti-endothelial cell antibodies on the interactions of leukocytes with vascular endothelial cells in vitro.
The role of mononuclear cells in antibody-mediated endothelial cell damage and vascular diseases is not well understood when compared to our understanding of the role of neutrophil-mediated endothelial injury in vascular diseases. Thus we initiated these in-vitro studies to investigate the interactions of leukocytes (neutrophils and mononuclear cells) with vascular endothelial cells in the presence and absence of antiendothelial cell antibodies (anti-red blood cell antiserum-anti-RBC). Cultured endothelial cells were isolated from bovine pulmonary artery. The effects of unfractionated and fractionated human leukocytes (neutrophils, mononuclear cells, or lymphocytes) on endothelial cell viability was examined both quantitatively (51Cr release) and qualitatively (electron microscopy). Results from these studies indicated that the interactions of mononuclear cells and lymphocytes with antibody-coated endothelial cells resulted in a significant endothelial cell lysis within 1 to 6 hours of reactions. Neutrophils, on the other hand, failed to induce significant endothelial cell damage compared to mononuclear cells and lymphocytes when tested under similar conditions. In the absence of anti-RBC antibodies, all cell types (neutrophils, mononuclear cells, or lymphocytes) did not produce detectable endothelial damage. Additionally, the effectiveness of mononuclear cells to injure antibody-labeled endothelial cells was confirmed by ultrastructural examination. Similar studies, utilizing leukocytes obtained from patients with atherosclerosis disease, were also undertaken. In these studies we found that, again, only mononuclear cells and lymphocytes wer capable of inducing damage to endothelial cells precoated with antibodies. In summary, our results demonstrate the ability of mononuclear cells and lymphocytes to induce significant damage to antibody-coated endothelial cells. This finding suggests a major role of mononuclear leukocytes in vascular endothelial destruction in diseases that are characterized by the presence of circulating autoantibodies in serum and the adhesion of mononuclear cells to the vascular wall. Such diseases include vasculitis, allograft rejection, serum sickness, and perhaps atherosclerosis particularly in patients with autoimmune diseases.
D000818:Animals; D000906:Antibodies; D002417:Cattle; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004727:Endothelium / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011651:Pulmonary Artery / Q000166:cytology; D014652:Vascular Diseases / Q000276:immunology / Q000473:pathology
D000906:Antibodies