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)

Thrombin stimulation of human platelets results in the release of a preformed proteinaceous human eosinophil (Eo)-chemotactic activity. By the use of different high-performance liquid chromatography techniques, two Eo-chemotactic polypeptides (EoCPs), tentatively termed EoCP-1 and EoCP-2, were purified to homogeneity. Upon SDS-PAGE analysis, these chemotaxins showed molecular masses near 8 kD. NH2-terminal amino acid sequence analysis revealed identical sequences for both EoCP-1 and EoCP-2, which are also identical to that of RANTES, a cytokine that structurally belongs to the interleukin 8 superfamily of leukocyte selective attractants, and that is known to be a "memory-type" T lymphocyte-selective attractant. In the major Eo chemotaxin, EoCP-1, the residues 4 and 5, which in EoCP-2 were found to be serine residues, could not be identified. Electrospray mass spectrometry (ESP-MS) of EoCPs revealed for EoCP-2 a molecular mass of 7,862.8 +/- 1.1 daltons, which is 15.8 mass units higher than the calculated value of RANTES, indicating that EoCP-2 is identical to the full-length cytokine, and oxygenation, probably at methionine residue number 64, has taken place. Upon ESP-MS, EoCP-1 showed an average molecular mass of 8,355 +/- 10 daltons, suggesting O-glycosylation at these serine residues. Both natural forms of RANTES showed strong Eo-chemotactic activity (ED50 = 2 nM) with optimal chemotactic migration at concentrations near 10 nM, however, there were no significant migratory responses with human neutrophils. Chemotactic activity of RANTES for human Eos could be confirmed using recombinant material, which has been found to be as active as the natural forms. Since RANTES gene expression has been detected in activated T lymphocytes, and recombinant RANTES was shown to be a "memory" T lymphocyte-selective attractant, it is now tempting to speculate about an important role of RANTES in clinical situations such as allergene-induced late-phase skin reactions in atopic subjects or asthma, where in affected tissues both memory T cells and Eos are characteristic.
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PMID:Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. 138 64

LD78 is a small secreted protein that has a sequence similar to a number of other polypeptides, including murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), interleukin 8 (IL-8), Act-2, monocyte chemoattractant protein 1 (MCP-1), and others. These polypeptides are members of a novel cytokine superfamily that is involved in the inflammatory response, wound healing, hematopoiesis, and tumorigenesis. Specific receptors for purified clonal LD78 protein were measured using four cell lines (HL-60, U937, Jurkat, and MJ). 125I-labeled recombinant LD78 bound most efficiently to U937 cells. We therefore characterized the receptors as being on the surface of U937 cells. Binding reached an equilibrium after incubation for 60 min at 4 degrees C. Scatchard analysis showed that there were two classes of binding sites on U937 cells, high affinity sites (Kd = 5.3 x 10(-9) M) and low affinity sites (Kd = 9.3 x 10(-8) M), with the average number of binding sites per cell being approximately 30,000 and approximately 90,000, respectively. These receptors for LD78 were distinct from the receptors for gamma-IFN and for IL-8. SDS-PAGE analysis of chemically crosslinked 125I-labeled LD78 receptor complexes identified a single band of 52 kDa. The ability to detect specific LD78 receptors should prove valuable in efforts to molecularly clone these receptors and to dissect the biological actions of LD78.
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PMID:Identification and characterization of specific receptors for the LD78 cytokine. 151 Nov 63

Injury to cartilage is a recognized sequela of neutrophil activation in arthritic joints. This study examined the possibility that chondrocytes may play a direct role in intraarticular neutrophil activation. We demonstrate that IL-1 beta-stimulated primary and subcultured human articular chondrocytes, express the gene for the potent neutrophil chemotactic and activating cytokine, IL-8. Expression of IL-8 mRNA is also inducible by TNF-alpha and LPS and, to a lesser degree, by the chondrocyte growth factor, transforming growth factor-beta, but not by platelet-derived growth factor, acidic and basic fibroblast growth factor, or epidermal growth factor. Analysis of IL-1 beta-stimulated cartilage organ cultures by in situ hybridization demonstrates that chondrocytes in all zones of cartilage are rapidly induced to express the IL-8 gene in high copy number. Metabolically labeled IL-1 beta-stimulated chondrocytes synthesize IL-8 de novo, which comigrates on SDS-PAGE with IL-8 produced by synovial fibroblasts. Furthermore, the conditioned media of IL-1 beta-stimulated chondrocytes and cartilage organ cultures contain neutrophil chemotactic activity which is completely neutralized by a specific antibody to IL-8, establishing that a bioactive form of IL-8 is the major secreted neutrophil chemotactic factor. By using a specific RIA, we demonstrate that not only IL-1 beta, but also TNF-alpha and LPS can induce abundant IL-8 secretion from chondrocytes. In conclusion, articular chondrocytes are readily inducible to express the IL-8 gene and secrete biologically active IL-8 which can promote neutrophil-mediated inflammation and cartilage destruction.
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PMID:Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. 172 66

A monocyte chemotactic and activating factor (MCAF) has been purified from TNF-stimulated 8387 human fibrosarcoma cell line-conditioned media. The purified MCAF showed microheterogeneity yielding two bands on SDS-PAGE analysis. Fibrosarcoma-derived MCAF specifically competed with THP-1 (a human monocytic cell line)-derived 125I-labeled MCAF in binding to human PBMC, whereas a similar basic heparin-binding leukocyte chemoattractant, IL-8, did not. The purified MCAF stimulated superoxide anion and N-acetyl beta-D glucosaminidase-releasing activity in human monocytes, as well as monocyte cytostatic augmenting activity against tumor cells and chemotactic activity for monocytes. When injected subcutaneously into Lewis rat ears, the purified human MCAF also induced considerable in vivo local monocyte infiltration beginning at 3 h and becoming maximal at 18 h. In conclusion, the data presented in this paper indicate that MCAF is a potent activator of monocytes as well as a monocyte recruitment factor that acts through receptors that are specific for this novel molecule. This novel cytokine might have an important role in tumor growth control due to its ability to attract and activate monocytes.
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PMID:Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. 216 98

Human dermal fibroblasts in culture secrete three protein-like neutrophil chemotactic factors, when stimulated either with human rIL-1 alpha or IL-1 beta; not, however, after incubation with LPS. These three fibroblast-derived neutrophil-activating proteins (FINAP) could be purified by subsequently performed reversed phase and size exclusion HPLC. By high resolution SDS-PAGE, all the proteins were shown to migrate with an Mr of 6,700 (alpha-FINAP), 3,600 (beta-FINAP), and 5,300 (gamma-FINAP). All purified cytokine preparations were found to be chemotactic for human neutrophils. In addition, all FINAP induced release of lysosomal enzymes in neutrophils. Deactivation of chemotaxin-elicitable enzyme release showed cross-desensitization of all FINAP with NAP-1/IL-8. Western blot analysis of alpha-FINAP by using mAb against neutrophil-activating protein (NAP)-1/IL-8 reveals immunologic cross-reactivity with NAP-1/IL-8. By amino-terminal amino acid sequence analysis alpha-FINAP could be identified as the 77-residue extended form of NAP-1/IL-8 containing the 79-residue form as a minor contaminant. Whereas beta-FINAP has been found to be a truncation product of alpha-FINAP, gamma-FINAP shows identity with authentic melanoma growth stimulatory activity with respect to retention time upon reversed phase HPLC, high resolution SDS-PAGE, and biologic properties, as well as amino-terminal amino acid sequence. These data show that human dermal fibroblasts may actively participate in inflammatory reactions by secretion of proinflammatory cytokines.
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PMID:IL-1 alpha or tumor necrosis factor-alpha stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. 217 8

Purification of monocyte-derived NAP-1/IL-8 by preparative reversed-phase (RP)-HPLC led to the detection of a second peak with polymorphonuclear leukocyte (PMNL)-activating (degranulation, chemotaxis) properties. The monokine responsible for this biological activity, which we tentatively termed NAP-3, could be purified to homogeneity by three different RP-HPLC steps. Tricine-SDS-PAGE analysis gave a single line at Mr 5.3 kD (NAP-1/IL-8 = 5.8 kD). NH2-terminal amino acid sequence analysis read as a major sequence (ASVATELRXCXLQT. .), which shows greater than 40% homology to that of NAP-1/IL-8. The sequence is identical to that found for the 13-kD moiety of melanoma growth stimulating activity (MGSA) and the product of the oncogene gro. Determination of neutrophil chemotactic activity of NAP-3 revealed a typical bell-shaped dose-response curve (ED50 = 2 ng/ml) with no significant neutrophil chemotactic activity at doses greater than 200 ng/ml. Also, in cytochalasin B-pretreated PMNL, NAP-3 elicited release of myeloperoxidase and beta-glucuronidase. Crossdesensitization studies in PMNL enzyme release revealed crossreactivities with the NAP-1/IL-8-R on PMNL. NAP-3 (MGSA/gro) appears to represent the first member of the novel supergene family of beta-thromboglobulin-like host defense cytokines, which expresses both mitogenic as well as proinflammatory properties at the nanogram level.
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PMID:Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. 218 61

A novel protein, NAP-4, could be isolated from human platelet lysates. NAP-4 preparations induced chemotaxis of human neutrophils with an ED50 near 400 ng/ml. Purification by anti NAP-1/IL-8 affinity chromatography and reversed phase HPLC revealed a single peak showing a single line upon SDS-PAGE corresponding to a Mr of 8000. NH2-terminal sequence analysis indicated an unique sequence showing strong homology to human platelet factor 4 and weak homology to tumor necrosis factor alpha as well. The most interesting finding is the absence of the first two cysteins, known to be strongly conserved in members of the family of platelet-factor 4-like host defense cytokines.
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PMID:Identification of a novel platelet-derived neutrophil-chemotactic polypeptide with structural homology to platelet-factor 4. 224 78

Stimulated human peripheral blood leukocytes produce a chemotactic factor for granulocytes (granulocyte chemotactic peptide/interleukin-8; GCP/IL-8), which is structurally related to platelet-derived beta-thromboglobulin. Analytically pure CGP/IL-8 and beta-thromboglobulin could be obtained after three purification steps, comprising adsorption to silicic acid, heparin-Sepharose chromatography and ion-exchange chromatography. Although GCP/IL-8 and beta-thromboglobulin had a similar affinity for heparin, they could be separated on a cation-exchange column. Both molecules were heterogeneous in that 6-7-kDa protein doublets were detected upon SDS/PAGE. N-terminal amino acid sequence analysis revealed the presence of six immunologically related but differently truncated polypeptides of beta-thromboglobulin, of which only two corresponded to previously described forms. Similarly, apart from a major polypeptide, five minor species of GCP/IL-8 were detected that also differed by N-terminal truncation. The most processed forms of beta-thromboglobulin and GCP/IL-8 were found to have their N-terminus in that region of the primary structure where a significant similarity between the two molecules starts. GCP/IL-8 was found to be chemotactic for granulocytes with a specific activity of 10(5) units/mg, whereas none of the beta-thromboglobulin species possessed detectable chemotactic activity.
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PMID:Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of beta-thromboglobulin. 252 1

Human umbilical vein endothelial cells in culture produce two chemotactic polypeptides when stimulated with LPS. The chemotactic factors could be purified to apparent homogeneity by HPLC techniques and were identified as 7.5-kDa and 15-kDa polypeptides by SDS-PAGE under nonreducing conditions. Both factors are potent chemotaxins for human neutrophils demonstrating half-maximal chemotaxis at 2 ng/ml and g ng/ml, respectively. In addition both peptides elicited release of azurophilic granule constituents when neutrophils were pretreated with cytochalasin B. Cross-desensitization experiments by using human neutrophils revealed cross-reactivities between both chemotaxins, not, however, with C5a or FMLP, indicating that both endothelial cell-derived neutrophil activating peptides (ENAP) are homologous. In addition, the 7.5-kDa factor (beta-ENAP) proved to be the quantitatively dominating and more potent chemotaxin as compared to the 15 kDa factor (alpha-ENAP). beta-ENAP shows biochemical and biologic similarities to monocyte- and lymphocyte-derived neutrophil-activating peptides MONAP and LYNAP, which recently were purified and sequenced.
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PMID:Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. 264 4

Specific receptors for a recently purified and cloned monocyte-derived neutrophil chemotactic factor (MDNCF) have been identified on the surface of normal human peripheral blood neutrophils using 125I-labeled recombinant human MDNCF (125I-MDNCF). Competitive binding of 125I-MDNCF to human neutrophils reached a maximal level at 1-3 h at 4 degrees C. The Scatchard analysis showed that there are approximately 20,000 receptors per cell with a single type of high affinity binding (Kd, 8 x 10(-10) M). The receptors for MDNCF are clearly distinct from the receptors for other cytokines and chemotactic agents, e.g., IL-1 alpha, TNF-alpha, and FMLP, C5a, leukotriene B4, and platelet activating factor. Based on the SDS-PAGE analysis of chemically crosslinked 125I-MDNCF receptor complex, there are two polypeptides that bind MDNCF; the molecular weight of these two MDNCF receptors were estimated to be 67,000 and 59,000. Treatment of a promyelocytic cell line, HL60, with 1.25% DMSO for 5 d in vitro increased the number of receptors up to 7,000 receptors/cell with a Kd of 1.2 x 10(-9) M.
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PMID:Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. 264 92


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