Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS.
Open accessAbstract
Lipoproteins isolated from normal human plasma can bind and neutralize bacterial lipopolysaccharide (LPS) and may represent an important mechanism in host defense against gram-negative septic shock. Recent studies have shown that experimentally elevating the levels of circulating high-density lipoproteins (HDL) provides protection against death in animal models of endotoxic shock. We sought to define the components of HDL that are required for neutralization of LPS. To accomplish this we have studied the functional neutralization of LPS by native and reconstituted HDL using a rapid assay that measures the CD14-dependent activation of leukocyte integrins on human neutrophils. We report here that reconstituted HDL particles (R-HDL), prepared from purified apolipoprotein A-I (apoA-I) combined with phospholipid and free cholesterol, are not sufficient to neutralize the biologic activity of LPS. However, addition of recombinant LPS binding protein (LBP), a protein known to transfer LPS to CD14 and enhance responses of cells to LPS, enabled prompt binding and neutralization of LPS by R-HDL. Thus, LBP appears capable of transferring LPS not only to CD14 but also to lipoprotein particles. In contrast with R-HDL, apoA-I containing lipoproteins (LpA-I) isolated from plasma by selected affinity immunosorption (SAIS) on an anti-apoA-I column, neutralized LPS without addition of exogenous LBP. Several lines of evidence demonstrated that LBP is a constituent of LpA-I in plasma. Passage of plasma over an anti-apoA-I column removed more than 99% of the LBP detectable by ELISA, whereas 31% of the LBP was recovered by elution of the column. Similarly, the ability of plasma to enable activation of neutrophils by LPS (LBP/Septin activity) was depleted and recovered by the same process. Furthermore, an immobilized anti-LBP monoclonal antibody coprecipitated apoA-I. The results described here suggest that in addition to its ability to transfer LPS to CD14, LBP may also transfer LPS to lipoproteins. Since LBP appears to be physically associated with lipoproteins in plasma, it is positioned to play an important role in the neutralization of LPS.
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A peripheral mechanism to inactivate lipopolysaccharide (LPS) is the loading of its lipid component onto lipoparticles.
“Because a peripheral mechanism to inactivate lipopolysaccharide (LPS) is the loading of its lipid component onto lipoparticles26”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [26]
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- Authors
- Wurfel, M. M., Kunitake, S. T., Lichenstein, H., Kane, J. P., & Wright, S. D.
- Affiliations
- Rockefeller University (US)
- ORCID
- Kane, J P
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-09-01
- Volume
- 180
- Issue
- 3
- Pages
- 1025-1035
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2191628
- OpenAlex
- W2169228758
- Cited by
- 442
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 17 · 2019: 3 · 2018: 11 · 2017: 7 · 2016: 15 · 2015: 16 · 2014: 18 · 2013: 10 · 2012: 9
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health (5r01ai030556-04)
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (AI 30556)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- lipopolysaccharide-binding protein, lipopolysaccharide neutralization, high-density lipoprotein, apolipoprotein A-I, CD14, endotoxic shock, gram-negative sepsis, neutrophil activation, serum lipoproteins
- MeSH terms
- Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Carrier Proteins, Humans, Lipopolysaccharides, Lipoproteins, Lipoproteins, HDL, Membrane Glycoproteins, Neutrophils, Plasma, Recombinant Proteins, Apolipoprotein A-I
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