UNIPROT:P10145 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complement plays an essential role in inflammation and tissue damage. However, it is largely unknown to what extent the system acts as a primary inducer of secondary mediator systems in the inflammatory network of human whole blood. Here we describe a novel in vitro model using the thrombin-specific hirudin analog lepirudin as anticoagulant, which, in contrast to heparin, did not interfere with complement activation. The model was used to study the role of complement in Escherichia coli-induced inflammatory responses. Granulocyte and monocyte oxidative burst was complement dependent as it was reduced by 85% and 70%, respectively, by the C3 [corrected] binding peptide compstatin. A similar reduction was found by inhibition of C5, C5a, and C5a receptor (C5aR). Furthermore, anti-CR3 antibodies were as efficient as the C5aR antagonist in reducing granulocyte oxidative burst, whereas blocking CD14 or C3aR had no effect. Up-regulation of granulocyte CR3 was virtually abolished by a C5aR antagonist. Opsonization and phagocytosis was completely inhibited by blocking of C5aR or CR3, whereas blocking of the FcgammaRs (CD16, CD32, CD64) had no effect. In contrast to oxidative burst and phagocytosis, cytokine secretion was largely complement independent. Thus, anti-CD14 abolished tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-10 secretion, whereas IL-8 was equally inhibited by anti-CD14 and compstatin. In conclusion, the present model is particularly useful for studying complement as part of the inflammatory network. The results emphasize a crucial role for C5a-C5aR interaction in E coli-induced up-regulation of CR3 and the subsequent oxidative burst and phagocytosis. Complement inhibition may have therapeutic implications in oxidative burst-induced tissue damage.
...
PMID:Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation. 1217 11

Pregnancy is characterized by the presence of generalized leukocyte activation. We used flow cytometry to investigate changes in phenotype and intracellular cytokines of circulating granulocytes, monocytes, and T lymphocytes of pregnant women during gestation. We report that peripheral circulation of pregnancy is characterized by an increased percentage of granulocytes and a decrease in lymphocytes. The proportion of monocytes remains stable throughout gestation; however, a progressive up-regulation of surface markers CD11a, CD54, and CD64 was detected. Monocytes also showed higher production of interleukin (IL)-12 and IL-1beta compared with the nonpregnant state, and granulocytes had greater potential to synthesize IL-8. All these changes were particularly marked in late gestation. T lymphocytes did not have any characteristics of the activated state and showed a decreased IL-6 production. These findings demonstrate that activation of maternal monocytes and granulocytes increases during pregnancy and support the idea that pregnancy results in an elevation of the innate immune system and suppression of the adaptive immune system.
...
PMID:Monocytes are progressively activated in the circulation of pregnant women. 1469 84

Poly(ethylene glycol):poly(acrylate) PEG-g-PA co-polymers were made that inhibited nonspecific protein and cellular adhesion. PEG-g-PA co-polymers were then covalently modified with either cell adhesion peptides or fragments of antibodies to monocyte/macrophage integrin receptors (anti-VLA4, anti-beta(1), anti-beta(2), and anti-CD64) known to enhance macrophage adhesion and, perhaps, modulate their activation. Peptides were either directly conjugated to the base material or linked by way of PEO-star tethers. Fragments of the antibody region containing the antigen-binding site (Fab' fragments) were coupled to other PEG-g-PA samples using the sulhydryl end groups on Fab' fragments to amine-bearing PEO stars. Macrophage adhesion rates, phagocytic response (oxidative burst), and cytokine expression were determined for each PEG-g-PA material. Luminol-enhanced chemiluminescence was used as a semiquantitative indication of monocyte-macrophage phagocytic activation (oxidative burst). Macrophage cytokine expression in response to control, base, and modified materials was determined by ELISAs for TNF-alpha, IL-1 beta, IL-6, and IL-8. Tissue culture poly(styrene) (TCPS)-mediated the greatest number of adherent monocyte/macrophage cells relative to PEG-g-PA materials. Both YRGDS and YEILDV peptides, whether directly or indirectly (via StarPEO) conjugated to PEG-g-PA, increased adhesion versus controls. Fab' fragments of all four antibodies also promoted enhanced adhesion versus controls. Fab'StarPEO materials presented two orders of magnitude fewer ligands per surface unit area than peptide star materials (10(8) vs. 10(10)), but were able to adhere similar numbers of cells. For surfaces presenting Fab'(VLA-4) or YEILDV, both of which may both bind to a cell's VLA-4 receptor, the Star:VLA4 surface showed a greater number of adherent monocyte/macrophages. This result suggests that the Fab' had a higher affinity to the cell receptor than a corresponding minimal peptide binding sequence. All materials exhibited low oxidative burst (luminescence counts per minute, LCPM) per cell DNA without the addition of exogenous stimuli (LCPM/DNA < 100). Directly conjugated peptide materials, poly(propylene) (PP), and TCPS showed the lowest levels of LCPM/DNA without the addition of exogenous stimulus (LCPM/DNA < 20). There was no correlation between LCPM/DNA ratios, with and without added LPS stimulus, versus the individual substrates. Monocyte/macrophages adherent to TCPS substrata showed the overall highest stimulatory potential in cytokine expression response to exogenous LPS, followed by PP > PEG-g-PA > StarPEO. Cells adherent to peptide-modified materials and Fab'-modified materials were overall less stimulated. The method of presenting the peptides (i.e., directly or via Star PEO) influenced the level of cytokine secreted by the adherent macrophage.
...
PMID:Monocyte/macrophage interactions with base and linear- and star-like PEG-modified PEG-poly(acrylic acid) co-polymers. 1283 32

Generation of antibodies against oxidized-low-density lipoproteins (oxLDL) during atherosclerosis could result in the formation and deposition of oxLDL immune complexes (oxLDL-IC) on the vascular endothelial cells. Inflammatory cells express scavenger receptor (SR such as CD36) and Fcgamma receptor (FcgammaR: CD32A and CD64) that can bind to oxLDL and oxLDL-IC, respectively. Hence, depending on anti-oxLDL IgG titer, circulating monocytes could adhere to endothelium to oxLDL-IC-coated vascular bed via either FcgammaR and/or CD36. In this study, we determined the relative contribution of SR and FcgammaR in mediating monocyte interaction with oxLDL-IC deposited on vascular bed. At saturating levels of anti-oxLDL IgG concentration, monocytic cells adhered to oxLDL-IC and this adhesion is completely blocked by anti-CD32A mAb. Using CHOK1-CD32A-CD36 cells expressing equal levels of CD32A and CD36, it was observed that at lower concentrations of anti-oxLDL IgG, CD32A and CD36 contribute about 75% and 25% of cell adhesion, respectively, while at higher concentrations of anti-oxLDL IgG the adhesion is completely CD32A-dependent. CD32A-dependent adhesion was further confirmed with peripheral blood monocytes and platelets that express 2- to 5-fold higher levels of CD36 compared to CD32A. Further, PBMC adhesion to oxLDL-IC-deposited endothelial cells induced secretion of pro-inflammatory chemokines, MCP-1 and IL-8. Our results demonstrate that anti-oxLDL IgG blocks oxLDL interaction with SR such as CD36, whereas oxLDL-IC formation promotes monocyte adhesion and subsequent chemokine release through FcgammaR. These findings suggest a role for FcgammaR-mediated inflammatory cell activation in the progression of atherosclerosis.
...
PMID:Anti-OxLDL IgG blocks OxLDL interaction with CD36, but promotes FcgammaR, CD32A-dependent inflammatory cell adhesion. 1708 22

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.
...
PMID:Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. 1736 39

Neonatal sepsis occurs from 1 to 21 newborns out of 1 000 live births with mortality rates as high as 30% up to 69%. The most important risk factors are prematurity, low birth weight, invasive medical procedure and prolonged hospitalization in neonatal intensive care units. An aimed and restrictive antibiotic therapy has an outstanding importance to reduce both morbidity-mortality rates and multiple drug-resistance. Generally, preterm newborns present nonspecific clinical signs of infection. The use of high sensitivity infection markers and a negative predictive value (near 100%) are important to distinguish infected and noninfected patients before the culture results and to verify adequacy and duration of antibiotic therapy. This article reviews the immunologic function and practical use of C reactive protein (CRP) and other markers in the diagnosis of neonatal sepsis. While CRP is a specific late infection marker, cytokines, cell surface markers and procalcitonin (PCT) are early infection markers. The use of multiple markers as CRP, PCT, IL-6, IL-8, CD64, CD11b is useful both to early (24-48 h) diagnose of neonatal sepsis, and to monitorate the antibiotic treatment while waiting for the results of cultural examinations.
...
PMID:[Evaluation of C reactive protein and others immunologic markers in the diagnosis of neonatal sepsis]. 1751 72

Neutrophil CD64 expression is a diagnostic marker for the early detection of bacterial infections. The aim was to investigate the kinetics of neutrophil CD64 expression during bacterial infection and the possible impact of surgical trauma. Blood samples were collected daily during 3 d after admission for analysis by flow cytometry of the surface expressions on neutrophils and monocytes of CD64, CD16, CD32, CD11b/CD18 and CD35, and analysis of serum CRP and blood WBC. Serum concentrations of IFNgamma, G-CSF, IL-6 and IL-8 were also analysed in adults. Eight children and 19 adult patients with bacterial infections, 12 patients admitted for hip-arthroplasty because of coxarthrosis and 30 healthy adults were studied. Neutrophil CD64 was increased all 3 d after start of treatment (p<0.0001) in children and adults with bacterial infections. The postoperative increase after surgery was less than the increase seen during bacterial infections (p<0.0001). CRP, G-CSF, IL-6 and IL-8 were raised both in bacterial infections and after surgery. Our results indicate that the expression of CD64 on neutrophils is a specific sign of bacterial infections. Neutrophil expression of CD64, therefore, seems to be a promising tool for the early detection of bacterial infections even during surgery.
...
PMID:Neutrophil CD64 (FcgammaRI) expression is a specific marker of bacterial infection: a study on the kinetics and the impact of major surgery. 1757 14

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.
...
PMID:Selective expansion of the CD14(+)/CD16(bright) subpopulation of circulating monocytes in patients with hemophagocytic syndrome. 1761 80

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.
...
PMID:Circulating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to interleukin-10. 1805 97

Non-specific markers of inflammation such as C-reactive protein (CRP) are associated statistically with an increased risk of atherosclerosis through mechanisms that have not yet been fully elucidated. We investigated the effects of CRP on several aspects of human monocyte biology, a cell type involved in the initiation and progression of atherosclerosis. Blood monocytes isolated from healthy men and premenopausal women (n = 9/group) were exposed to purified CRP (25 microg/ml) for 12 hours. Changes in gene expression were analyzed using a custom-made array containing oligonucleotide sequences of 250 genes expressed by activated monocytes and confirmed by quantitative PCR. CRP increased significantly the expression of the cytokines interleukin (IL)-1alpha, IL-1beta and IL-6, and the chemokines GRO-alpha, GRO-beta and IL-8. CRP also displayed anti-inflammatory effects through upregulation of liver X receptor (LXR) alpha and activin receptor expression, and down-regulation of alpha 2-macroglobulin expression. Increased LXRalpha mRNA expression in both monocytes and the monocytic cell lineTHP-1 was associated with increased LXRalpha protein expression and nuclear translocation, as well as increased ABCA1 mRNA expression, a target gene of LXRalpha. Western blot analysis revealed CRP-induced nuclear translocation of NF-kappaB and activation of p42/44, MAP and Akt kinases. CRP-induced LXRalpha mRNA expression was inhibited by anti-CD64 (FcgammaRI) antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating study demonstrates that CRP modulates the expression of genes that contribute to both pro- and anti-inflammatory responses in human monocytes. Among these novel anti-inflammatory effects, we show clearly that CRP activates the LXRalpha pathway.
...
PMID:C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor alpha, on human monocytes. 1832 90

<< Previous 1 2 3 4 5 Next >>