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Updated: Mar 16, 2026
In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
Published on: November 10, 2011
Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density
Zhili Yao1, Jessica M Mates1, Alana M Cheplowitz1
1Department of Internal Medicine, The Ohio State University, Columbus, OH 43210;
Abstract:
During Gram-negative bacterial infections, excessive LPS induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2-4 min in mice, and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ∼75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ∼25% with KC. Notably, the ratio of LSEC-KC-associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor C, an LPS binding protein, competitively inhibits high-density lipoprotein (HDL)-mediated LPS association with LSEC early in the process. Supporting the previous notion, 3 min postinfusion, 75% of infused fluorescently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis.
Insights
Liver sinusoidal endothelial cells (LSEC) rapidly clear lipopolysaccharide (LPS) from circulation, challenging the traditional view of Kupffer cells (KC). High-density lipoprotein (HDL) further facilitates this LPS clearance process.
Area of Science:
- Immunology
- Hepatology
- Microbiology
Background:
- Gram-negative bacterial infections trigger inflammation and sepsis through lipopolysaccharide (LPS) acting on immune cells.
- The liver is known to clear LPS from circulation, a process traditionally attributed solely to Kupffer cells (KC).
- Existing understanding posits liver clearance of LPS as a slow process mediated exclusively by KC.
Purpose of the Study:
- To investigate the rapid clearance kinetics of LPS from circulation.
- To determine the specific liver cell types involved in LPS uptake and processing.
- To elucidate the role of high-density lipoprotein (HDL) in LPS clearance.
Main Methods:
- Utilized microscopic techniques with fluorescently tagged LPS to track its distribution in the liver.
- Employed kinetic analysis of LPS bioactivity using a modified limulus amebocyte lysate assay.
- Investigated the interaction of LPS-HDL complexes with liver cells.
Main Results:
- LPS demonstrated rapid clearance from circulation with a half-life of 2-4 minutes in mice.
- Liver sinusoidal endothelial cells (LSEC) were found to associate with approximately 75% of the cleared LPS, significantly more than Kupffer cells (KC) (∼25%).
- High-density lipoprotein (HDL) was identified to facilitate LPS association with LSEC, suggesting a key role in clearance.
Conclusions:
- LSEC play a dominant and rapid role in clearing LPS from the circulation, challenging the exclusive role of KC.
- HDL actively participates in LPS clearance by promoting its association with LSEC.
- This LSEC and HDL-mediated clearance pathway offers a potential strategy to mitigate sepsis-induced inflammation.
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