Interactions of bacterial lipopolysaccharides with tissue macrophages and plasma lipoproteins.
Several of the cellular and molecular interactions of LPS within the experimental host have been examined in an attempt to elucidate the potential role of these interactions in initiating the pathophysiologic events of endotoxemia. Using 125I-LPS, the clearance of LPS from the blood and its tissue, cellular and subcellular localization was established. The H-Mø was found to be the major host site of intravenous LPS localization and, subsequently, the effect of LPS on explanted H-Mø was demonstrated to be both directly cytotoxic and stimulatory of a selective increase in several cellular enzymes. Both the depression in H-Mø function and the stimulation of release of local and systemic mediators by LPS give the H-Mø a potential central role in initiating endotoxemic shock and DIC. Finally, the marked reduction in the clearance rate of LPS remaining in plasma after the initial rapid tissue localization was found to coincide with a density shift to less than 1.2 g/cm3 for the parent LPS. This density shift was found to be dependent upon binding of the LPS to HDL in the serum or plasma and, with the presence of cellular HDL receptors, accounts for a shift in tissue localization to the adrenals. A postulated effect of direct adrenal damage by LPS can thus be invoked as contributing to the endotoxemic syndrome.
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli; D005966:Glucuronidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000166:cytology*; D008264:Macrophages / Q000187:drug effects*; D008657:Metabolic Clearance Rate; D010587:Phagocytosis / Q000187:drug effects; D011817:Rabbits; D012475:Salmonella
D008070:Lipopolysaccharides; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D007770:L-Lactate Dehydrogenase; D000135:Acid Phosphatase; D005966:Glucuronidase