Endotoxin-induced endothelial injury and subendothelial accumulation of fibronectin in rat aorta.
Endotoxin (lipopolysaccharide, LPS) induces endothelial injury in arterial vessels. Fibronectin is known to be involved in cell attachment and wound repair. The present study was designed to elucidate the effect of LPS on the production and distribution of fibronectin in relation to injury and repair in rat aortic endothelium. Male Sprague-Dawley rats were sacrificed for ultrastructural and immunocytochemical evaluations at 1, 3, 6, 24, and 48 hr after a single intravenous injection of 1.5 or 3 mg/kg body weight E. coli LPS. Apparent morphological signs of endothelial injury, including cell detachment, denudation, cell death, and edema were observed 1-48 hr after injection. Parietal thrombosis and leukocyte diapedesis were also observed in the aorta. A profound increase in subendothelial fibronectin was found following LPS treatment. However, no distinct change in intracellular fibronectin was observed in the same endothelium until 24 hr after injection. Using horseradish peroxidase (HRP) and anti-fibronectin-HRP antibody as tracers, LPS was also found to increase permeability and extravasation of plasma proteins (fibronectin) of the aortic endothelium. The increase of subendothelial fibronectin possibly resulted from increased influx and sequestration of plasma fibronectin. This increase may provide a firm substratum for reendothelialization after vascular injury.
Kang
Y H
YH
Pathophysiology Division, Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
Williams
R
R
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001345:Autoradiography; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005353:Fibronectins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D005353:Fibronectins