Amazoniac
Member
http://www.ncbi.nlm.nih.gov/pubmed/15949133
"Animals that cannot sense endotoxin may die if they are infected by Gram-negative bacteria.
Animals that sense endotoxin and respond too vigorously may also die, victims of their own
inflammatory reactions."
"Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS) has no enzymatic or other intrinsic activity; the ‘toxicity’ of LPS is conferred entirely by the animal that senses its presence and reacts to it in injurious ways."
"The known endotoxin detoxification mechanisms may be grouped into four categories: (i) molecules that bind LPS and prevent it from engaging TLR4; (ii) enzymes that degrade the lipid A moiety in ways that decrease its activity; (iii) inactivation following uptake into the liver and spleen; and (iv) adaptations that modify target cell responses to LPS."
"…these antibodies often bind LPS O-antigens rather than the more conserved, but less accessible, core or lipid A structures."
"Plasma lipoproteins. When LPS is injected intravenously into experimental animals, many of the LPS molecules bind quickly to circulating lipoproteins and are slowly cleared from the circulation by tissues that express specific lipoprotein receptors. Lipoprotein-bound LPS does not stimulate cells, suggesting that the lipid A moiety inserts into lipoprotein particles in such a way that it is no longer exposed. Transfer of LPS from bacterial membranes to lipoproteins is promoted by certain plasma proteins, including phospholipid transfer protein and, especially, LBP."
"LPS binding to different lipoprotein species correlates with the lipoprotein’s content of phospholipid, which is found on the particle surface. The ultimate fate of the LPS–lipoprotein particle is determined largely by its apolipoprotein content, however; particles that contain apoA-1 bind to SR-B1 receptors on various cells, whereas apoE-rich particles are more likely to be taken up via the LDL receptor or lipoprotein receptor-related protein (LRP) VLDL receptor on hepatocytes. ApoE–/– mice are more susceptible to LPS-induced lethality than are normal mice; infusion of chylomicrons or VLDL, which contain apoE, can protect experimental animals from LPS challenge. One plausible protective mechanism is suggested by apoE’s ability to deliver LPS to hepatocytes, bypassing cytokine-producing Kupffer cells and inducing tolerance in the liver. Infusing HDL has also been protective in some animal models."
"In rodents or rabbits, the liver quickly removes as much as 40–50% of an intravenous dose of LPS from the bloodstream. Most of the available evidence suggests that it is initially taken up by Kupffer cells and then moves into hepatocytes. Intact Gram-negative bacteria are even more completely removed from the circulation by the liver and, to a lesser extent, the spleen."
"There is evidence that the hepatic sinusoids are perfused, more or less continuously, with endotoxin-laden blood from the GI tract, and that the liver effectively filters this endotoxin from the bloodstream without reacting to it."
"Cells that have been exposed to low concentrations of LPS typically undergo a series of adaptations that alter their responses to a second exposure. Although the molecular basis for this ‘acute endotoxin tolerance’ is not well understood, recent studies point to an intracellular phosphatase, SHIP, as a necessary intermediate. When tolerant cells sense LPS a second time, some responses may increase (e.g. the production of IL-1Ra), while others decrease (TNF, IL-6, and IL-1(R)production)."
I'll probably select more passages from it soon..
"Animals that cannot sense endotoxin may die if they are infected by Gram-negative bacteria.
Animals that sense endotoxin and respond too vigorously may also die, victims of their own
inflammatory reactions."
"Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS) has no enzymatic or other intrinsic activity; the ‘toxicity’ of LPS is conferred entirely by the animal that senses its presence and reacts to it in injurious ways."
"The known endotoxin detoxification mechanisms may be grouped into four categories: (i) molecules that bind LPS and prevent it from engaging TLR4; (ii) enzymes that degrade the lipid A moiety in ways that decrease its activity; (iii) inactivation following uptake into the liver and spleen; and (iv) adaptations that modify target cell responses to LPS."
"…these antibodies often bind LPS O-antigens rather than the more conserved, but less accessible, core or lipid A structures."
"Plasma lipoproteins. When LPS is injected intravenously into experimental animals, many of the LPS molecules bind quickly to circulating lipoproteins and are slowly cleared from the circulation by tissues that express specific lipoprotein receptors. Lipoprotein-bound LPS does not stimulate cells, suggesting that the lipid A moiety inserts into lipoprotein particles in such a way that it is no longer exposed. Transfer of LPS from bacterial membranes to lipoproteins is promoted by certain plasma proteins, including phospholipid transfer protein and, especially, LBP."
"LPS binding to different lipoprotein species correlates with the lipoprotein’s content of phospholipid, which is found on the particle surface. The ultimate fate of the LPS–lipoprotein particle is determined largely by its apolipoprotein content, however; particles that contain apoA-1 bind to SR-B1 receptors on various cells, whereas apoE-rich particles are more likely to be taken up via the LDL receptor or lipoprotein receptor-related protein (LRP) VLDL receptor on hepatocytes. ApoE–/– mice are more susceptible to LPS-induced lethality than are normal mice; infusion of chylomicrons or VLDL, which contain apoE, can protect experimental animals from LPS challenge. One plausible protective mechanism is suggested by apoE’s ability to deliver LPS to hepatocytes, bypassing cytokine-producing Kupffer cells and inducing tolerance in the liver. Infusing HDL has also been protective in some animal models."
"In rodents or rabbits, the liver quickly removes as much as 40–50% of an intravenous dose of LPS from the bloodstream. Most of the available evidence suggests that it is initially taken up by Kupffer cells and then moves into hepatocytes. Intact Gram-negative bacteria are even more completely removed from the circulation by the liver and, to a lesser extent, the spleen."
"There is evidence that the hepatic sinusoids are perfused, more or less continuously, with endotoxin-laden blood from the GI tract, and that the liver effectively filters this endotoxin from the bloodstream without reacting to it."
"Cells that have been exposed to low concentrations of LPS typically undergo a series of adaptations that alter their responses to a second exposure. Although the molecular basis for this ‘acute endotoxin tolerance’ is not well understood, recent studies point to an intracellular phosphatase, SHIP, as a necessary intermediate. When tolerant cells sense LPS a second time, some responses may increase (e.g. the production of IL-1Ra), while others decrease (TNF, IL-6, and IL-1(R)production)."
I'll probably select more passages from it soon..
