CD14 employs hydrophilic regions to "capture" lipopolysaccharides

被引:56
作者
Cunningham, MD
Shapiro, RA
Seachord, C
Ratcliffe, K
Cassiano, L
Darveau, RP
机构
[1] Univ Washington, Hlth Sci Ctr, Dept Periodont, Seattle, WA 98195 USA
[2] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA
[3] Immunex Corp, Seattle, WA 98101 USA
[4] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA
关键词
D O I
10.4049/jimmunol.164.6.3255
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD14 participates in the host innate inflammatory response to bacterial LPS obtained from Escherichia coli and other Gram-negative bacteria. Evidence from several laboratories suggests that different regions of the amino-terminal portion of the molecule may be involved in LPS binding. In this report a series of single-residue serine replacement and charge reversal mutations were generated to further elucidate the mechanism by which this protein may bind a multitude of different LPS ligands, Single-residue CD14 mutation proteins were examined for their ability to bind LPS obtained from E. coli, Porphyromonas gingivalis, and Helicobacter pylori and facilitate the activation of E-selectin from human endothelial cells. In addition, the single-residue CD14 mutation proteins were employed to perform monoclonal epitope-mapping studies with three LPS-blocking Abs that bound tertiary epitopes, Evidence that several different hydrophilic regions of the amino-terminal region of CD14 are involved in LPS binding was obtained. Epitope-mapping studies revealed that these hydrophilic regions are located on one side of the protein surface. These studies suggest that CD14 employs a charged surface in a manor similar to the macrophage scavenger receptor to "capture" LPS ligands and "present" them to other components of the innate host defense system.
引用
收藏
页码:3255 / 3263
页数:9
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