Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Yu, Bo; Hailman, Eric; Wright, Samuel D.

doi:10.1172/jci119160

Cited by 217 publications

(163 citation statements)

References 25 publications

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“…We have previously observed that the fluorescence of FITC-LPS is enhanced when LBP complexes to the LPS (7), and others have observed the same phenomenon with Bodipy-LPS (8). Based on the sedimentation properties of LPS-LBP complexes, we have speculated that the increase in fluorescence was due to a reduction in fluorescein self-quenching resulting from disaggregation of LPS by LBP (7).…”

Section: Comparison Of Effects Of Lbp and Bpi On Fitc-lps-mentioning

confidence: 61%

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Tobias

Soldau

Iovine

et al. 1997

Journal of Biological Chemistry

119

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Lipopolysaccharide (LPS)-binding protein (LBP) andbactericidal/permeability-increasing protein (BPI) are closely related LPS-binding proteins whose binding to LPS has markedly different functional consequences. To gain better insight into the possible basis of these functional differences, the physical properties of LBP-LPS and BPI-LPS complexes have been compared in this study by sedimentation, light scattering, and fluorescence analyses. These studies reveal dramatic differences in the physical properties of LPS complexed to LBP versus BPI. They suggest that of the two proteins, only LBP can disperse LPS aggegates. However, BPI can enhance both the sedimentation velocity and apparent size of LPS aggregates while inhibiting LPS-LBP binding even at very low (1:40 to 1:20) BPI:LPS molar ratios.The lipopolysaccharide (LPS)-binding protein 1 (LBP) and the bactericidal/permeability-increasing protein (BPI) are both LPS-interactive mammalian proteins with approximately 45% amino acid sequence identity (1, 2). LPS is considered to be the principal component of Gram-negative bacteria that alerts the host to invading bacteria and triggers defensive responses (3, 4). These responses are usually beneficial and effective but may also become excessive and lead to endotoxic shock (3-5). Both LBP and BPI modulate the bioactivity of LPS (2,3,5). LBP is a plasma protein that catalyzes the transfer of LPS from LPS aggregates to other LPS-binding proteins (3, 6 -9). Prominent among these is CD14, a surface molecule of myeloid cells that is also present in the circulation as a soluble protein. LBP and CD14 together represent the main pathway by which cells recognize low concentrations of LPS and are stimulated to respond to 10,11). In contrast to the LPS-stimulatory properties of LBP, binding of LPS by BPI results in inhibition of the bioactivities of LPS (2). BPI is produced by polymorphonuclear leukocytes and stored in its azurophilic granules (12, 13). It contributes substantially to both the intracellular and extracellular antibacterial activity of polymorphonuclear leukocyte-rich inflammatory exudates toward Gram-negative bacteria (14, 15). The high affinity of BPI for LPS accounts for the target-cell specificity of the antibiotic activity of BPI for Gram-negative bacteria (2, 16). In contrast to BPI, binding of LBP to bacterial envelope LPS does not produce detectable membrane alterations or other antibacterial effects.We have recently described the use of fluorescein-labeled LPS (FITC-LPS) as well as metabolically labeled ([ 3 H]LPS) and sucrose density gradients to characterize the formation and physical properties of complexes of LPS with LBP and the soluble form of CD14 (7). In this report we describe results obtained by studying the binding of FITC-LPS and [ 3 H]LPS to BPI using the techniques described earlier and in addition compare the effects of LBP and BPI on the light scattering properties of LPS. The results obtained reveal striking differences in the physical properties of LBP-LPS and BPI-LPS complexes. Thus, un...

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Section: Comparison Of Effects Of Lbp and Bpi On Fitc-lps-mentioning

confidence: 61%

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Tobias

Soldau

Iovine

et al. 1997

Journal of Biological Chemistry

119

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“…There are controversial reports of the linkage between H. pylori infection and atherosclerosis [18]. sCD14 contributes to lipid metabolism, as sCD14 transports lipids and LPS to high-density lipoprotein (HDL) [31,32]. Dysfunctional lipid metabolism is a characteristic feature of several infections [33].…”

Section: Discussionmentioning

confidence: 99%

Effect of CD14 promoter polymorphism andH. pyloriinfection and its clinical outcomes on circulating CD14

Karhukorpi¹,

Yan²,

Niemelä

et al. 2002

Clinical and Experimental Immunology

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SUMMARYCD14 is a pattern recognition receptor on the membranes of monocytes and macrophages for several microbial products, of which lipopolysaccharide (LPS) is the best known. A shed form of CD14 is present in serum. As the CD14 gene promoter polymorphism -159C/T and some bacterial infections may affect the sCD14 levels, we compared the impact of both the CD14 promoter polymorphism and Helicobacter pylori infection on serum sCD14 levels in 201 dyspeptic patients (group 1) who had undergone gastroscopy, and 127 staff members (group 2) with no endoscopy. sCD14 was measured from the sera by a commercial enzyme immunoassay (EIA), and CD14 genotyping was carried out with PCR. Helicobacter pylori infection was detected by serology and/or culture or PCR. sCD14 levels were elevated in the subjects carrying the T allele (CT or TT genotype) in both groups when compared with subjects with the CC genotype. Overall, H. pylori-positive subjects tended to have higher sCD14 levels compared with H. pylori-negative subjects. In group 1 consisting of dyspeptic patients, those with gastric ulcer, gastric erosion or duodenal ulcer had significantly elevated levels of sCD14 compared with the patients with normal endoscopic findings or macroscopic gastritis. The recent use of NSAIDs was also associated with enhanced sCD14. Thus, we were able to show several factors, one genetic and the other environmental (H. pylori infection and mucosal lesion), to have an impact on sCD14.

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“…The role of CD14, LBP, and TLRs in LPS signaling has been well supported by studies in animal models (13)(14)(15)(16). Besides its function in endotoxin signaling, it has been proposed that CD14 is involved in transportation of other lipids (17,18), cell-cell interaction during different immune responses (19 -21), and recognition of apoptotic cells (22,23). Therefore, CD14 becomes an interesting molecule to investigate in various biological processes.…”

mentioning

confidence: 98%

Hepatocytes Contribute to Soluble CD14 Production, and CD14 Expression Is Differentially Regulated in Hepatocytes and Monocytes

Pan¹,

Zhou²,

Hetherington³

et al. 2000

Journal of Biological Chemistry

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CD14 presents as a glycosylphosphatidylinositollinked membrane protein on the surface of monocytes/ macrophages and as a soluble protein in the serum. Our previous studies have shown that an 80-kilobase pair (kb) genomic DNA fragment containing the human CD14 gene is sufficient to direct CD14 expression in a monocyte-specific manner in transgenic mice. In addition, we discovered that human CD14 is highly expressed in hepatocytes. Here, we report the generation of transgenic mice with either a 24-or 33-kb human CD14 genomic DNA fragment. Data from multiple transgenic lines show that neither the 24-nor the 33-kb transgenic mice express human CD14 in monocytes/macrophages. However, human CD14 is highly expressed in the liver of the 33-kb transgenic mice. These results demonstrate that human CD14 expression is regulated differently in monocytes and hepatocytes. Furthermore, we identified an upstream regulatory element beyond the 24-kb region, but within the 33-kb region of the human CD14 gene, which is critical for CD14 expression in hepatocytes, but not in monocytes/macrophages. Most importantly, the data demonstrate that the liver is one of the major organs for the production of soluble CD14. These transgenic mice provide an excellent system to further explore the functions of soluble CD14.Every year septic shock promoted by Gram-negative bacteria causes over 100,000 deaths in the United States (1, 2). Lipopolysaccharide (LPS), 1 an endotoxin of Gram-negative bacteria, is known to be responsible for initiating host responses leading to septic shock (3). LPS stimulates its response by inducing the host cells to produce and release endogenous mediators including the proinflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-␣ (4). Lipopolysaccharidebinding protein (LBP), CD14, and Toll-like receptors (TLRs) are mediators of LPS stimulation (5-10). There are two forms of CD14. One is the glycosylphosphatidylinositol-anchored membrane CD14 (mCD14) found mainly on the surface of cells of myeloid lineage. The other is soluble CD14 (sCD14), found in the serum and urine (11,12). LPS binds to CD14 in the presence of an acute phase response protein LBP. This complex mediates sepsis through TLRs. The role of CD14, LBP, and TLRs in LPS signaling has been well supported by studies in animal models (13)(14)(15)(16). Besides its function in endotoxin signaling, it has been proposed that CD14 is involved in transportation of other lipids (17, 18), cell-cell interaction during different immune responses (19 -21), and recognition of apoptotic cells (22,23). Therefore, CD14 becomes an interesting molecule to investigate in various biological processes.CD14 is highly expressed on the surface of monocytes/macrophages and strongly up-regulated during the differentiation of monocytic precursor cells into mature monocytes (24 -26). Therefore, CD14 has been commonly used as a differentiation marker for monocytes/macrophages. CD14 serves as an excellent model for the study of monocytic gene regulation and lineage dif...

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Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Cited by 217 publications

References 25 publications

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Lipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS

Effect of CD14 promoter polymorphism andH. pyloriinfection and its clinical outcomes on circulating CD14

Hepatocytes Contribute to Soluble CD14 Production, and CD14 Expression Is Differentially Regulated in Hepatocytes and Monocytes

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