ApoM binds endotoxin contributing to neutralization and clearance by High Density Lipoprotein.
Level 5 - mechanism / opinion, no new human data
In vitro binding assays, cell culture experiments, and computational modeling (bench research)
PubMed 36915826 · doi:10.1016/j.bbrep.2023.101445
What was done
The authors examined whether apolipoprotein M (ApoM) binds bacterial endotoxin (lipopolysaccharide, LPS) and assists in high-density lipoprotein (HDL)-mediated neutralization. Isothermal titration calorimetry (ITC) was used to measure binding thermodynamics between ultrapure *E. coli* LPS and recombinant human ApoM. Computational docking simulations were performed to model structural binding sites. In vitro macrophage assays (using human THP-1 cells and murine macrophages) evaluated LPS neutralization and TNFα release following treatment with purified human HDL and recombinant ApoM.
What was found
ITC demonstrated that ApoM binds *E. coli* LPS in a 1:1 stoichiometry with high affinity (dissociation constant Kd < 1 μM). The interaction was enthalpy-driven and exothermic (ΔrH = -36.5 kJ/mol). Computational docking predicted that LPS docks near the calyx region of ApoM without blocking its binding pocket. In human THP-1 macrophages, purified HDL neutralized *E. coli* LPS activity and significantly suppressed LPS-induced TNFα release (exact numerical percentage or fold reduction was not provided in the abstract).
Why it matters
This study identifies a direct biophysical interaction between ApoM and endotoxin, providing a mechanistic explanation for how HDL binds, neutralizes, and clears LPS during systemic inflammation or sepsis.
Limits
The study is limited entirely to in vitro biophysical assays, cell culture models, and in silico docking, lacking in vivo pharmacokinetic, clearance, or survival data in animal models of endotoxemia or sepsis. The abstract reports no exact quantitative values or effect sizes for the reduction of TNFα in cell culture.
Cited by
- supports All classes of plasma lipoproteins are capable of binding bacterial lipopolysaccharide (endotoxin).