Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons.
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PMID:Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8. 218 41

We have tested the possible physical interactions between the iC3b receptor (CR3), lymphocyte function-associated Ag-1, and class III Fc gamma receptor (Fc gamma RIII) at neutrophil surfaces. Cells were labeled using fluorochrome-conjugated Fab or F(ab')2 fragments of antireceptor mAb. Labeled receptors were capped using second-step F(ab')2 fragments of goat anti-mouse Fab antiserum. After 20 min at 37 degrees C, 68% of the cells capped the anti-CR3 plus second-step complex. Capping was time, temperature, and cytochalasin B sensitive. When capped cells were probed with Fab' or F(ab')2 fragments of anti-Fc gamma RIII labeled with a distinct fluorochrome, 41% of the cells cocapped Fc gamma RIII. Indistinguishable results were obtained when potential antibody combining sites within caps were blocked with a large excess of Fab or F(ab')2 fragments. When Fc gamma RIII was capped, 49% of the cells cocapped CR3. Similarly, LFA-1 cocapped with both CR3 and Fc gamma RIII. Importantly, other membrane components including HLA class I, Mo5, CD13, CR type 1, and IL-8 receptors and N-4-nitrobenzo-2-oxa-1, 3-diszole L-alpha-dimyristoyl phosphatidylethanolamine did not cocap with CR3. However, the positive control Con A did cocap with CR3 and Fc gamma RIII. We next evaluated the effect of saccharides on CR3-Fc gamma RIII cocapping and found that 0.15 M N-acetyl-D-glucosamine (NADG), alpha-methyl-D-mannoside, and D-mannose significantly inhibited cocapping by 70, 58, and 48%, respectively. No inhibition was obtained using glucose, galactose, N-acetyl-neuraminic acid, fucose, sorbitol, fructose, or sucrose. Similarly, Fc gamma RIII-lymphocyte function-associated-1 cocapping was inhibited by NADG. However, the cocapping of CR3 with lymphocyte function-associated-1 or Con A were not affected by 0.15 M NADG, which suggests that NADG inhibition of leukoadhesin-Fc gamma RIII cocapping is not due to a general effect of NADG on capping. Inasmuch as Fc gamma RIII is a glycophospholipid-linked membrane protein, we speculate that it interacts with CR3 and/or lymphocyte function-associated-1 via lectin-like interactions.
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PMID:Cocapping of the leukoadhesin molecules complement receptor type 3 and lymphocyte function-associated antigen-1 with Fc gamma receptor III on human neutrophils. Possible role of lectin-like interactions. 768 Oct 86

1. The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins. Recently we succeeded in cloning some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). 2. G. cydonium contains several lectins and cDNA for two of them (termed LECT-1 and LECT-2) was cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Next, we have isolated and characterized a cDNA coding for a receptor tyrosine kinase of class II (GCTK). The deduced amino acid sequence shows two characteristic domains: i) the tyrosine kinase domain and ii) an immunoglobulin-like domain. The latter part shows high homology to the vertebrate type immunoglobulin domain. This result, together with the lectin data, demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. 3. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen, a "homeotic" organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain sequence was successful. The deduced amino acid sequence of G. cydonium showed high homology to chicken and to the Antennapedia sequence from Drosophila melanogaster. 4. These data support the view that the kingdom Animalia is of monophyletic origin.
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PMID:On the monophyletic evolution of the metazoa. 778 92

The marine sponge Geodia cydonium contains several lectins. The main component, called lectin-1, is composed of three to four identical subunits. The subunits of the lectins were cloned from a cDNA library; two clones were obtained. From the deduced aa sequence of one clone, LECT-1, a mol. wt of 15,313 Da is calculated; this value is in good agreement with mass spectrometric analysis of 15,453 +/- 25 Da. The sequence of another clone, LECT-2, was analysed and the aa sequence was deduced (15,433 Da). The two subunits have a framework sequence of 38 conserved aa which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Clustering of lectin sequences of various species following their pairwise comparison establishes a dendrogram, which reveals that the sponge lectin could be considered as the ancestor for vertebrate S-type lectins.
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PMID:S-type lectins occur also in invertebrates: high conservation of the carbohydrate recognition domain in the lectin genes from the marine sponge Geodia cydonium. 791 39

A neutrophil migration-inducing protein has been isolated from the saline extract of Artocarpus integrifolia seeds by successive sugar affinity chromatography steps during which the protein was not absorbed by D-galactose resin, and then was absorbed to and eluted from D-mannose resin by 0.1 M D-mannose. Gel filtration on Superdex 75 HR indicated a molecular mass of 52 kDa when 0.1 M D-mannose was present in the elution buffer. A single band of apparent molecular mass of 13 kDa was demonstrable by SDS-PAGE only after heating, both in the presence and absence of reducing agent, suggesting that the molecule is a tetramer formed by the noncovalent association of 13 kDa chains. Isoelectric forms corresponding to isoelectric points of 4.0, 4.2, 5.0, and 5.2 were demonstrable by isoelectric focusing-PAGE, and four active forms having the same isoelectric points were separated by chromatofocusing. The minimal m.w. calculated from amino acid analysis data was 13,193. The protein, denoted KM+, stimulated neutrophil migration in the rat peritoneal cavity assay in a dose-related manner in the range of 1 to 300 micrograms per rat. The dose-response curve of the in vitro chemotactic activity of KM+ was bell shaped and its ascending limb was dose dependent in the range of 1 ng to 10 micrograms/well. D-Mannose (0.1 M) inhibited the in vitro (80%) and in vivo (60%) neutrophil migration-inducing activities of KM+ and also its hemmaglutinating activity. The chemotactic activity was shown to be caused by haptotaxis rather than chemokinesis. The physical and biologic properties of KM+ suggest that this lectin may attract neutrophils by a mechanism involving a haptotactic gradient as has been proposed for IL-8. KM+ might be used as tool to study protein-carbohydrate interactions during neutrophil migration through the extracellular matrix.
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PMID:A neutrophil migration-inducing lectin from Artocarpus integrifolia. 804 46

We characterized the immunophenotype as well as functional properties--phagocytosis, the uptake of acetylated LDL, and the expression of HLA class II antigens, adhesion molecules, and cytokine mRNA--of fibroblast-like synoviocytes from rheumatoid arthritis synovium. Skin fibroblasts (FB) and umbilical vein endothelial cells (HUVEC) were studied in parallel. Cytofluorometric immunophenotyping by use of 84 mAb and 2 lectins and immunofluorescence microscopy indicated a high degree of homology between the three cell types. Only staining with mAb to von Willebrand factor (vWF) and CD31 and the lectin UEA-I appeared specific to HUVEC, whereas the mAb 5B5 to prolyl 4-hydroxylase that has been reported to be specific to FB stained HUVEC as well as synoviocytes and FB. All of the cells phagocytosed fluorescent latex beads of 1.7 and 2.6 microns in size. The uptake of acetylated LDL could be shown by HUVEC and, surprisingly, by synoviocytes, but not by FB. The induction of HLA-DR, -DP, and -DQ by IFN-gamma on the three cell types showed a similar dose-dependence. The upregulation of ICAM-1 by IL-1 alpha, TNF-alpha, and IFN-gamma appeared similar, whereas the induction of VCAM-1 by IL-1 alpha, IL-4, TNF-alpha, and IFN-gamma showed differences between the three cell types. ELAM-1 was expressed only on HUVEC after treatment with IL-1 alpha and TNF-alpha. The capacity of the cells to produce cytokines was studied at the level of mRNA by reverse transcription and PCR. All three cell types expressed the mRNA of IL-1 alpha, IL-6, IL-8, GM-CSF, and TGF-beta 1 spontaneously or after LPS stimulation, but never TNF-alpha mRNA. Our results indicate a high degree of relationship between the three cell types. In contrast to HUVEC, none of the markers and functional properties investigated appear specific to FB. Therefore, the issue of the origin of fibroblast-like synoviocytes and the role of vascular endothelial cells in the inflamed synovium is discussed.
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PMID:Characterization of the immunophenotype and functional properties of fibroblast-like synoviocytes in comparison to skin fibroblasts and umbilical vein endothelial cells. 808 88

The type III-B Fcgamma receptor (FcgammaRIII-B) is a glycosyl-phosphatidylinositol-linked receptor found on human neutrophils. A soluble form of FcgammaRIII-B (sCD16) corresponding to the extracellular region of the receptor circulates in plasma. In the present work, we have identified membrane receptors for sCD16. Soluble CD16 bound to CR3 (CDllb/CD18)- and CR4 (CDllc/CD18)- positive leukocytes and cell lines, the labeling was inhibited by anti-CD11b, CD11c or CD18 mAbs, and the up-regulation of CR3 and CR4 led to an increased fixation of sCD16. Transfected eukaryotic cells expressing recombinant CD11b/CD18 or CD11c/CD18 heterodimers but not those expressing CD11a/CD18 bound sCD16. Moreover, the lectin-like binding site of CR3 is probably involved in the interaction with sCD16, as suggested by inhibition studies using mAbs against CR3 or sugars such as N-acetyl D-glucosamine, alpha- or beta-methyl D-glucoside, alpha- or beta-methyl D-mannoside, or zymosan. Thus, the complement receptors CR3 and CR4 are membrane receptors for sCD16. Through this interaction, sCD16 induces a CR3-dependent production of IL-6 and IL-8 by monocytes. These results suggest that sCD16 plays a regulatory role in inflammatory processes and provide a molecular basis for the interaction between FcgammaRIII-B and CR3 described on the cell membrane.
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PMID:Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors. 875 24

In this study we examined the mechanisms by which glomerular mesangial cells ingest apoptotic cells and the mesangial cell response to this event, since there is in vivo evidence that such semiprofessional phagocytes participate in phagocytic clearance of both apoptotic leukocytes and apoptotic resident cells from inflamed glomeruli, thereby promoting resolution of glomerulonephritis. Mesangial cell phagocytosis of apoptotic neutrophils in vitro was not affected by inhibitors of lectin-like receptors, phosphatidylserine receptors, the 61D3 Ag, and beta1 and beta2 integrins, receptors which have been implicated in phagocytosis of apoptotic cells by particular populations of semiprofessional and professional phagocytes. However, the specific inhibitory effects of cationic aminosugars, Arg-Gly-Asp-Ser (RGDS) peptide, and mAbs to phagocyte alpha(v)beta3 vitronectin receptor integrin and "bridging" thrombospondin 1 (TSP1) indicated that mesangial cell phagocytosis of apoptotic cells involved an alpha(v)beta3/TSP mechanism akin to that described for human monocyte-derived macrophages (Mphi) in which Mphi CD36 plays an important role in binding "bridging" TSP1. However, mesangial cells did not express CD36 and there was no evidence for involvement of alternative phagocyte receptors for TSP1, heparan sulfate proteoglycan and sulfatides. Nevertheless, phagocytosis of apoptotic neutrophils by either mesangial cells or Mphi failed to elicit secretion of IL-8 and MCP-1, representatives of each major class of proinflammatory chemotactic cytokines. We conclude that mesangial cell phagocytosis of apoptotic neutrophils involves a novel CD36-independent, alpha(v)beta3/TSP-mediated mechanism that is uncoupled from chemokine secretion, emphasizing the injury-limiting potential of mesangial cell phagocytosis of apoptotic cells.
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PMID:Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: mediation by a novel CD36-independent vitronectin receptor/thrombospondin recognition mechanism that is uncoupled from chemokine secretion. 912 3

Entamoeba histolytica can cause invasive disease by disruption of the intestinal barriers and subsequent lysis of the intestinal cells. Adherence to and contact dependent killing of host cells requires the galactose inhibitable lectin. To elucidate the mechanism whereby E. histolytica influences host defence, the authors assessed the change of proinflammatory cytokine genes expressed by colon epithelial cells in response to co-culture with E. histolytica trophozoites and carbohydrates, including galactose, N-acetyl-galactosamine or N-acetyl-lactosamine, which prevented E. histolytica from attaching to epithelial cells. After HT-29 human colon epithelial cells were co-cultured with E. histolytica trophozoites in the presence or absence of carbohydrates (0.1-100 mM), RNA was extracted from the epithelial cells by an acid guanidinium thiocyanate-phenol-chloroform method. Cytokine gene expression was assessed by quantitative RT-PCR using a synthetic internal standard, and proteins were determined by ELISA. IL-8 mRNA expressed by HT-29 cells in response to E. histolytica trophozoites was downregulated in the presence of galactose, N-acetylgalactosamine or N-acetyl-lactosamine (0.1-100 mM), and this was paralleled by decreased IL-8 protein secretion. GM-CSF and IL-1 alpha/beta mRNAs were also downregulated in those cells in the presence of these agents. These results suggest that the expression of proinflammatory cytokine genes could be inhibited by preventing E. histolytica from attaching to the host's colon epithelial cells.
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PMID:Cytokine genes are down-regulated when attachment of Entamoeba histolytica to HT-29 colon epithelial cells is prevented. 920

The gastric mucosa of normal rats exhibits no detectable inflammation or visible damage. We examined the effect of the gastric mucosal extract of rats on neutrophil chemotaxis and tried to purify antichemotactic factor. The chemotaxis of neutrophils was examined by the modified Boyden's method. After mucosal layer was scraped and then homogenized and centrifuged at 20,000 x g for 30 min, the supernatant was used as rat gastric mucosal extract (RGME). Prior exposure of neutrophils to the gastric mucosal extract caused a dose-dependent reduction in the neutrophil migration induced by formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) and interleukin 8 (IL-8) without affecting the cell viability. The antichemotactic factor was partially purified by lectin affinity chromatography on wheat germ lectin (WGL)-Sepharose, anion exchange chromatography on Mono-Q and gel filtration on Superose 12. The molecular weight of the antichemotactic factor was estimated to be around 60 k by gel filtration. The activity was markedly abolished by boiling for 5 min, heating at 60 degrees C for 30 min, and treatment with 1% acetic acid, 0.1 M Na2CO3 or trypsin. Furthermore, the FMLP-induced migration of neutrophils pretreated with the antichemotactic factor for 5 min followed by washing with fresh medium was inhibited, although the factor was not added to the chamber. These results suggest that the gastric mucosa of rats intrinsically generates an antichemotactic factor which might play a crucial role in maintenance of the integrity of the gastric mucosa.
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PMID:Characterization of antichemotactic factor extracted from the gastric mucosa of rats. 944 23


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