Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma levels of procalcitonin (PCT) are increased in patients with severe bacterial infections. Its cellular origin and potential pathophysiological function in sepsis is, however, unclear. White blood cells have recently been described to express both PCT mRNA and protein. The aim of this study was to determine whether PCT has any influence on the surface expression of receptors, relevant in inflammation, on human whole blood leukocytes under normal and septic conditions. Venous blood from healthy donors was incubated with PCT (40 ng/ml or 1200 ng/ml) alone or in combination with lipopolysaccharide (LPS, 10 ng/ml) or peptidoglycan (PepG, 10 micrograms/ml) for 6 h. The surface expression of CD14, CD54, CD64, CD80, CD86 and HLA-DR was determined by flow cytometry. We could not detect any influence of PCT on the expression of these receptors. Further studies on potential effects on other cell types during infection seem warranted.
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PMID:Procalcitonin does not influence the surface expression of inflammatory receptors on whole blood leukocytes. 1139 89

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.
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PMID:Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. 1174 32

The present study was conducted to investigate if proteinase-3 (PR3) is able to influence lipopolysaccharide (LPS) responses of monocytes via degradation of CD14 and if antineutrophil cytoplasmic antibodies (ANCA) may modify this process. Recombinant (r) CD14 and CD14 expressed on monocytes were investigated for PR3 mediated degradation by SDS-PAGE and FACS analysis, respectively. TNF-alpha production in whole blood was used to determine functional consequences of CD14 degradation. PR3 degraded rCD14 in a dose- and time-dependent fashion. Major degradation products were found with apparent molecular weight of 45, 25 and 10 kDa. Treatment of PR3 with PMSF completely abolished CD14 degradation. ANCA IgG did not inhibit CD14 degradation. In whole blood, addition of PR3 resulted in diminished CD14 expression on monocytes. In contrast, CD14 was increased in a subpopulation of cells that expressed major histocompatibility (MHC) class II and PR3, but lacked expression of CD64 and CD16. LPS mediated TNF-alpha production in whole blood was significantly inhibited when preincubated with PR3. This study demonstrates that PR3 can degrade rCD14 and that PR3 differentially affects CD14 expression in subsets of monocytes. ANCA IgG does not play a significant role herein.
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PMID:Human proteinase 3 can inhibits LPS-mediated TNF-alpha production through CD14 degradation: lack of influence of antineutrophil cytoplasmic antibodies. 1206 99

Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily and is readily detected in certain cancer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell responses to a T helper cell type 2 phenotype. In this study, we further asked its ability to modulate CD14+ monocyte differentiation into macrophages induced by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able to modulate the expression of several macrophage markers, including CD14, CD16, CD64, and human leukocyte antigen-DR. In contrast, the expression of CD11c, CD36, CD68, and CD206 (mannose receptor) was not affected in the in vitro culture system. Moreover, phagocytic activity toward immune complexes and apoptotic bodies as well as the production of free radicals and proinflammatory cytokines in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte-derived macrophages. This suggests that DcR3.Fc might have potent, suppressive effects to down-regulate the host-immune system.
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PMID:Modulation of macrophage differentiation and activation by decoy receptor 3. 1465 14

Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.
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PMID:Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome. 1604 54

Persistent, localized Staphylococcus aureus infections, refractory to antibiotic treatment, can result in massive tissue destruction and surgical intervention is often the only therapeutic option. In that context, we investigated patients with S. aureus-induced infection at various sites, apparent as either olecranon bursitis, empyema of the knee joint or soft tissue abscess formation. As expected, a prominent leucocyte infiltrate was found, consisting predominantly of polymorphonuclear neutrophils (PMN) (up to 75%) and to a lesser extent of T lymphocytes and natural killer (NK) cells. In line with their bactericidal capacity, PMN expressed the high-affinity receptor for IgG, CD64 and the lipopolysaccharide (LPS) receptor CD14; moreover, the oxygen radical production in response to the bacterial peptide f-MLP was enhanced, while chemotactic activity was greatly reduced. The more intriguing finding, however, was that a portion of PMN had acquired major histocompatibility complex (MHC) class II antigens and CD83, indicative of a transdifferentiation of PMN to cells with dendritic-like characteristics. Of note is that a similar transdifferentiation can be induced in PMN in vitro, e.g. by gamma interferon or by tumour necrosis factor alpha. Co-cultivation of transdifferentiated PMN with autologous T lymphocytes resulted in prominent T cell proliferation, provided that S. aureus enterotoxin A was added. Taken together, persistent S. aureus infection induces PMN to acquire characteristics of dendritic cells, which in turn might promote the local immune response.
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PMID:Cellular inflammatory response to persistent localized Staphylococcus aureus infection: phenotypical and functional characterization of polymorphonuclear neutrophils (PMN). 1636 36

Monocytes constitute 5-10% of total human peripheral blood leucocytes and remain in circulation for several days before replenishing the tissue macrophage populations. Monocytes display heterogeneity in size, granularity and nuclear morphology, and in the expression of cell membrane molecules, such as CD14, CD16, CD32, CD64, major histocompatibility complex class II, CCR2, CCR5, among others. This has led to the suggestion that individual monocyte/macrophage populations have specialized functions within their microenvironments. This study provides evidence for the occurrence of two peripheral blood monocyte subpopulations on the basis of their differential expression of GM1, a sphingolipid found mostly in lipid rafts, a CD14(+) GM1(low) population and a CD14(+) GM1(high) population comprising about 97.5% and 2.5% of total CD14(+) cells, respectively. GM1 expression correlates with functional differences in terms of endocytic activity, susceptibility to mycobacterial infection, and response to lipopolysaccharide (LPS) (modulation of Toll-like receptor-4 expression). CD14(+) GM1(low) cells proved to be less endocytic and more responsive to LPS, whereas CD14(+) GM1(high) cells are more endocytic and less responsive to LPS. In addition, during monocyte to macrophage differentiation in vitro, the percentage of CD14(+) GM1(high) cells increases from about 2.5% at day 1 to more than 50% at day 7 of culture. These results suggest that GM1(low) and GM1(high) monocytes in peripheral blood, represent either different stages of maturation or different subsets with specialized activities. The expression of CD16 on GM1(high) favours the first possibility and, on the other hand that up-regulation of GM1 expression and probably lipid rafts function is involved in the monocyte to macrophage differentiation process.
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PMID:Expression of GM1, a marker of lipid rafts, defines two subsets of human monocytes with differential endocytic capacity and lipopolysaccharide responsiveness. 1725 May 89

Overproduction of proinflammatory cytokines is characteristic of hemophagocytic syndrome (HPS), a highly lethal inflammatory disease. Peripheral blood monocytes include two distinct subpopulations according to surface antigen expression: a major type, CD14(+)/CD16(-) (classical monocytes), and a minor type, CD14(+)/CD16(bright) (proinflammatory monocytes). Among peripheral blood monocytes from HPS patients, CD14(+)/CD16(bright) cells were increased, together with lipopolysaccharide-induced production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. By three-color immunofluorescence, CD14(+)/CD16(bright) monocytes exhibited more intense human leukocytic antigen DR than CD14(+)/CD16(-) monocytes, consistent with greater maturity. Serum IL-6, TNF-alpha, and IL-8 were increased in HPS patients. A sensitive inflammatory marker, neutrophil CD64 expression, also was significantly elevated in HPS patients. In conclusion, expansion of proinflammatory monocytes and increased expression of neutrophil CD64 appeared to be important in the pathophysiology of HPS. Expansion of CD14(+)/CD16(bright) monocytes and neutrophil CD64 expression could serve as indicators of the inflammatory state in HPS.
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PMID:Selective expansion of the CD14(+)/CD16(bright) subpopulation of circulating monocytes in patients with hemophagocytic syndrome. 1761 80

CD64 is a high-affinity Fc(gamma)RI receptor expressed by activated neutrophils that has been recently evaluated as a potential sepsis parameter. In the present study, the kinetics of neutrophil membrane CD64 expression were examined during a standardized inflammatory response, using a human endotoxemia model, and compared with hematological indices, CRP, cytokines and interleukins. Ten healthy subjects received 2 ng/kg intravenous Escherichia coli lipopolysaccharide (LPS). After administration of LPS, neutrophil CD64 showed a biphasic response, characterized by a first increase from 108.5 +/- 7.5 to 133 +/- 6 AFU after 1 h (P = 0.047) and a second increase that started at 6 h and reached its maximum of 167 +/- 13 AFU at 22 h (P < 0.0001). CRP concentrations increased to 40 +/- 5 mg/dl 22 h after the administration of LPS. The cytokines and interleukins reached their maximum response within 1-2 h. The maximum values of pro-inflammatory cytokines (TNF-alpha, IFN-gamma and IL-6) correlated with the CD64 expression at 22 h after LPS administration (r(2) = 0.76, r(2) = 0.78, r(2) = 0.81, respectively, all P < 0.05), whereas this correlation was not found for the anti-inflammatory IL-10 (r(2) = 0.058, P = 0.54), suggesting that neutrophil CD64 expression might be a quantitative marker for innate immunity that could easily be used in the clinical setting.
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PMID:Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia. 1762 50

We compared blood neutrophils (PMNs) collected from healthy subjects with PMNs derived from either blood or airways collected from the same cystic fibrosis (CF) patients. When compared to healthy blood PMNs, CF blood PMNs expressed enhanced level of CD64, a marker of neutrophil activation, and lower level of Toll-like receptor-2 (TLR2). CF airway PMNs expressed enhanced level of TLR4. Interleukin-8 (IL-8) production by CF blood PMNs could be enhanced upon addition of lipopolysaccharide or peptidoglycan, and this production was inhibited by recombinant human IL-10. In contrast, CF airway PMNs released spontaneously high level of IL-8 that was neither further enhanced by microbial activators nor inhibited by recombinant human IL-10. The levels of IL-10 receptors were similar in all types of neutrophils. These data further demonstrate that circulating PMNs from CF patients display a distinct pattern of surface markers, including TLRs, as compared to PMNs from healthy donors, and that airways PMNs from CF patients are primed and resistant to anti-inflammatory signals delivered by IL-10.
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PMID:Circulating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to interleukin-10. 1805 97


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