| Information |
|---|
| lipopolysaccharide-binding protein precursor |
| InnateImmunity |
|
chr20 (+) (chr20:36408299-36439067) |
|
NM_004139
|
| 77 |
| 0 |
| 2 |
| 0 |
|
[ SNPper ]
[ GoldenPath ]
[ Gene Image ]
[ LocusLink ]
[ Omim ]
[ PubMed ]
|
|
Responses of inflammatory cells to subpicomolar concentrations of bacterial pathogens require the cooperation between CD14 and LBP, a lipid transfer protein that recognizes lipid A, the biologically active moiety of endotoxin. LBP facilitates the binding of LPS to soluble CD14 or membrane CD14 and plays a critical role in the CD14-dependent clearance of bacteria from the circulation. However, LBP does not seem to participate directly in initiating signal transduction. BPI is a 456-residue cationic protein produced only by precursors of neutrophils and is stored in the primary granules of these cells. The potent cytotoxicity of BPI is limited to gram-negative bacteria, reflecting the high affinity (<10 nM) of BPI for bacterial LPS. The biological effects of isolated BPI are linked to complex formation with LPS. Binding of BPI to live bacteria via LPS causes immediate growth arrest. Actual killing coincides with later damage to the inner membrane. Complex formation of BPI with cell-associated or cell-free LPS inhibits all LPS-induced host cell responses. BPI and LBP are members of a family of structurally and functionally related proteins. The members of this family, including cholesteryl ester transfer protein and phospholipid transfer protein, are highly conserved at the mRNA and protein levels, suggesting biological importance of the transfer lipid-like structures in aqueous environments, which has been identified as their main function. The BPI and LBP genes were both localized to human chromosome 20, and their genomic structures are almost identical.
Common nucleotide exchanges with a frequency of more than 1%, have been identified in both BPI and LBP. The respective genotype frequencies were analyzed in a group of patients with sepsis (n=204), compared with control probands (n=250). The association to unfavorable outcome was also assessed. Common polymorphisms in the gene for LBP in combination with male gender were found to be associated with an increased risk for the development of sepsis and, furthermore, may be linked to an unfavorable outcome. These data support the important immunomodulatory role of LBP in Gram-negative sepsis and suggest that genetic testing may be helpful for the identification of patients with an unfavorable response to Gram-negative infection. By contrast, the same study did not show any association of the polymorphisms of BPI that were analyzed with either the incidence or outcome of sepsis.
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