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Gram negative bacteria naturally release endotoxins which are lipopolysaccharide molecules. These molecules are toxic to many eukaryote cells, including macrophages. My question is how animal organisms locate, isolate, contain these toxic molecules. For example, if a lipopolysaccharide attaches to a macrophage, thus neutralizing it, does this actually kill the macrophage or just render it inert? In any case, the ineffective macrophage must now be removed as waste. How does that occur?

In the Wikipedia article on endotoxin it reads "Normal human blood serum contains anti-LOS antibodies..." without further describing them. I find this statement strange because normally when I think of antibodies, I think of them attacking cells or organisms, not individual molecules like lipopolysaccharides. What are these anti-LOS antibodies and how do they function?

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    $\begingroup$ There are a lot of questions in this post. I went ahead and answered what I read as the central question, but you should consider making separate posts for your other questions re: macrophage killing, dead macrophage clearance, anti-LOS antibodies, etc. $\endgroup$ – MikeyC Jul 7 at 17:05
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There are too many questions embeded here to cover in a single answer. I'll summarize and answer what I interpret to be the "central" question.

How do animals A) locate, B) isolate, and C) contain/eliminate bacterial endotoxins?

LPS in the blood stream is rapidly bound by LPS-binding protein (LBP) and localized to the liver for detoxification and excretion (1).

A) LBP recognizes and binds the Lipid-A region of the LPS molecule (2),

B) At this point LPS is released from bacterial cell membrane and sequestered into complexes with high-density lipoprotein (HDL). This is also the stage at which free LPS can activate CD14+ monocytes, triggering an acute inflammation response (3). However, additional HDL reduces monocyte activation, suggesting that these complexes inactivate LPS by "isolating" it from CD14 (4).

C) Finally, the LPS-HDL complex is taken up by the liver, either into Kupffer Cells (~25%) or liver sinusoidal endothelial cells (~75%), where enzymatic inactivation of LPS occurs either by dephosphorylation of the phosphates or deacetylation of the primary acyl components of lipid A (5)

Given the hydrophobic characteristics of LPS lipid-A and the fact that it's processed in the liver, I suspect that LPS and its metabolites are eliminated from the body via excretion into the bile ducts, but I haven't found a reference in the literature to confirm that suspicion.

References:

  1. Wassenaar and Zimmermann, Eur J Microbiol Immunol. 2018 Sep 28; 8(3): 63–69.
  2. Tobias et al., J Biol Chem. 1989 Jun 25;264(18):10867-71.
  3. Vesy et al., Infect Immun. 2000 May; 68(5): 2410–2417.
  4. Flegel et al, Infect Immun. 1989 Jul; 57(7): 2237–2245.
  5. Yao et al. J Immunol. 2016 Sep 15; 197(6): 2390–2399.
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