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)

The present study demonstrates that tumour necrosis factor (TNF) and FMLP, but not IL-1 or IL-8, enhanced the adherence of polymorphonuclear neutrophil (PMN) to fibronectin, an extracellular matrix protein. The adherence induced by FMLP was very rapid, within 5 min while the induction of adherence by TNF was much slower, reaching maximum at 60 min. TNF also enhanced an adhesion of PMN to other extracellular matrix proteins, such as laminin, collagen IV and gelatin II, but not to human serum albumin. Anti-CD18 MoAb completely inhibited the binding of TNF-stimulated PMN to fibronectin and partially inhibited the binding to laminin. Further investigation showed that adhesion of TNF-stimulated PMN to fibronectin and laminin was inhibited by anti-CD11b MoAb and to a lesser extent by CD11a MoAb. In contrast to TNF-stimulated PMN the binding of unstimulated PMN to fibronectin and laminin was only inhibited by anti-CD11a MoAb. Anti-CD11c had no effect on PMN adherence. These results suggest that unstimulated PMN adhere to extracellular proteins through the CD11a/18, while TNF-stimulated PMN adhere through the CD11b/18. These results suggest that TNF secreted at the site of inflammation may enhance the interaction of PMN with the extravascular environment through the CD11b/18 complex.
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PMID:Human polymorphonuclear leucocytes stimulated by tumour necrosis factor-alpha show increased adherence to extracellular matrix proteins which is mediated via the CD11b/18 complex. 135 90

Neutrophils from patients suffering from severe congenital neutropenia (SCN), who were receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF), were investigated in order to analyze the previously described decrease in chemotaxis. This study demonstrated the decreased chemotaxis to five well-known chemoattractants, FMLP, C5a, IL-8, LTB4 and PAF. To further investigate this impairment of patients' neutrophils, receptors and receptor turnover for chemoattractants were examined using flow cytometry. We found 1) increased FMLP receptor and decreased C5a receptor expression, 2) a normal expression of intracellular FMLP receptors after incubation with PMA, 3) increased loss and decreased re-expression of FMLP receptors after incubation with this peptide, 4) normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1 (CD11a/CD18), 5) further signs of in vivo preactivation: high expression of Fc gamma-RI (CD64) and Fc gamma-RII (CD32), decreased expression of Fc gamma-RIII (CD16), increased expression of CD14, and low expression of HLA-DR. These data demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is not due: a) to a decrease in the number of intra- or extracellular FMLP receptors; b) to a decrease of adhesion molecules. However, the decreased chemotaxis could result from an altered FMLP receptor turnover. The relevance of the altered Fc gamma-receptor pattern for the in vivo occurrence of side-effects, e.g. the necrotic vasculitis, of G-CSF treatment is discussed.
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PMID:Altered function and surface marker expression of neutrophils induced by rhG-CSF treatment in severe congenital neutropenia. 137 Apr 19

We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.
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PMID:In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions. 138 98

Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.
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PMID:Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on synovial fluid neutrophils from patients with inflammatory joint disease. 139 30

Gro beta and IL-8 are two members of the small induced secreted (SIS) cytokine family (C-X-C subgroup) with proinflammatory activities on neutrophils. In order to assess whether or not the interaction with their receptors results in similar biological actions, we compared the two cytokines in five different bioassays. Gro beta showed similar biological activities as IL-8 in tests of chemotaxis, induction of the respiratory burst, and induction of interleukin 6 (IL-6) production. However, for two other biological activities: augmentation of the expression of CD11b on the cell surface and rapid elevation of the intracellular calcium concentration, maximal effects required 100 times more gro beta than IL-8. Taken together, these results suggest that the stimulation of the IL-8 or gro beta receptor evokes three similar responses, but that only the activation of the IL-8 receptor and not that of gro beta results in elevated CD11b expression and calcium mobilization in human neutrophils.
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PMID:The biological activities of gro beta and IL-8 on human neutrophils are overlapping but not identical. 147 97

Several structural homologues of the chemotactic peptide neutrophil-activating peptide 1/IL-8 (NAP-1/IL-8) were tested for their ability to influence the expression and function of adhesion-promoting receptors on human polymorphonuclear leukocytes (PMN). NAP-2, melanoma growth stimulatory activity, and two forms of NAP-1/IL-8 (ser-NAP-1/IL-8 and ala-NAP-1/IL-8, consisting of 72 and 77 amino acids, respectively), each caused an increase in the expression of CD11b/CD18 (CR3) and CR1, which was accompanied by a decrease in the expression of leukocyte adhesion molecule-1 (LAM-1, LECAM-1). The binding activity of CD11b/CD18 was also enhanced 3- to 10-fold by these peptides, but enhanced function was transient: binding of erythrocytes coated with C3bi reached a maximum by 30 min and declined thereafter. Ser-NAP-1/IL-8, ala-NAP-1/IL-8, NAP-2, and melanoma growth stimulatory activity also caused a two- to threefold enhancement of the phagocytosis of IgG-coated erythrocytes (EIgG) by PMN without causing a large increase in the expression of Fc gamma receptors. Enhanced phagocytosis of EIgG appeared to be mediated through CD11b/CD18, because F(ab')2 fragments of an antibody directed against CD18 inhibited NAP-1/IL-8-stimulated ingestion of EIgG. The four active peptides caused a rapid, transient increase in the amount of F-actin within PMN, indicating that they are capable of influencing the structure of the microfilamentous cytoskeleton, which participates in phagocytosis. Two other NAP-1/IL-8-related peptides, platelet factor 4 and connective tissue-activating peptide III, were without effect on expression of CD11b/CD18, CR1, and LAM-1, binding activity of CD11b/CD18, or Fc-mediated phagocytosis, and increased actin polymerization only slightly. Our observations indicate that several members of the NAP-1/IL-8 family of peptides were capable of promoting integrin-mediated adhesion and Fc-mediated phagocytosis, processes important in the recruitment of PMN to sites of inflammation and antimicrobial responses of PMN.
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PMID:Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis. 172 41

Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF-alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation.
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PMID:Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism. 193 64

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.
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PMID:Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. 196 19

We have investigated mechanisms that regulate the generation of IL-8 by human neutrophils on contact with zymosan particles in vitro. Zymosan stimulated IL-8 production, which increased with increasing particle numbers and was abolished by the protein synthesis inhibitor cycloheximide. IL-8 was detectable in culture supernatant at 8 h reaching a maximum at 24 h. In all further experiments IL-8 was measured at 24 h. mAbs to neutrophil CD18 (60.3 and 6.5E) caused a marked suppression of IL-8 generation, but only if added up to 2 h after zymosan stimulation. An anti-CD11b mAb (KIM 225) substantially inhibited zymosan-induced IL-8 release. We investigated whether other mediators generated during phagocytosis modulate IL-8 production. Two selective platelet-activating factor (PAF) receptor antagonists, WEB 2086 and UK 74505, produced a profound suppression of IL-8 generation, when added within 30 min to 1 h of zymosan stimulation. An IL-1R antagonist, a leukotriene B4 antagonist, and an anti-TNF-alpha Ab had no effect on IL-8 generation. FMLP, PAF, and a stable PAF agonist did not stimulate significant IL-8 production, however, a calcium ionophore (A23187) did induce IL-8 release and this was suppressed by UK 74505. We conclude that zymosan-induced IL-8 generation involves stimulation of the neutrophil via a CD11b/CD18 receptor resulting in beta 2-integrin mediated activation of signal transduction mechanisms that leads to cytokine synthesis. Furthermore, endogenously generated PAF, or a PAF, or a PAF-like molecule, appears to have an autocrine function in regulating this pathway of IL-8 production at an early stage after the interaction between the neutrophil and the particles.
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PMID:Zymosan-induced IL-8 release from human neutrophils involves activation via the CD11b/CD18 receptor and endogenous platelet-activating factor as an autocrine modulator. 751 37

Selective eosinophil recruitment occurs after experimental Ag challenge and in tissue sites of allergic diseases. The mechanisms of selective eosinophil migration are still unknown. In our study, we examined the ability of chemokines to induce transendothelial migration (TEM) of eosinophils in vitro. Among the chemokines tested, only RANTES induced eosinophil TEM. RANTES failed to induce TEM of neutrophils. Interestingly, IL-8 induced neutrophil TEM and had no effect on eosinophil TEM. RANTES-induced TEM was concentration-dependent and was inhibited by Abs directed against the beta 2 integrin CD18. When IL-1-activated endothelial cells were utilized, RANTES-induced TEM also involved the eosinophil beta 1 integrin VLA-4. RANTES did not increase eosinophil adhesion to either resting or IL-1-activated endothelial cells, nor did the chemokine increase CD11b or decrease L-selectin expression. A gradient of RANTES appears to be required for eosinophil TEM. Pre-exposure of eosinophils to IL-5 dramatically potentiated the TEM response to RANTES. These findings suggest that the chemokine RANTES is a potent and selective inducer of eosinophil TEM. Because RANTES appears to be produced in vivo during allergic reactions or in allergic diseases, we speculate that these findings may have some direct relevance to the mechanism of selective eosinophil recruitment in vivo in humans.
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PMID:Eosinophil transendothelial migration induced by cytokines. III. Effect of the chemokine RANTES. 751 42


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