Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased numbers of eosinophils are found in parasitic infections, autoimmune diseases and allergic diseases such as allergic asthma. They are activated by distinct cytokines and chemokines leading to the immigration in the inflamed tissue and mediate tissue damage by releasing reactive oxygen species. Here, the effect of the recently cloned CC chemokine human eotaxin was investigated for its ability to affect different eosinophil effector functions and compared to the CC chemokines MCP-3 and RANTES. Human eotaxin induced chemotaxis of human eosinophils in a dose-dependent manner. The range of efficacy of the CC chemokines compared to the well-known chemotaxin C5a was eotaxin = RANTES > MCP-3 = C5a. In addition, eotaxin induced rapid and transient actin polymerization, a prerequisite for cell migration, in eosinophils in the same range of efficacy as observed for chemotaxis. To investigate whether eotaxin was able to activate the respiratory burst of eosinophils, release of reactive oxygen species was measured by lucigenin-dependent chemiluminescence. Eotaxin induced production of significantly high amounts of reactive oxygen species at a concentration between 10 ng/ml and 500 ng/ml. Surprisingly, the effect of eotaxin was comparable to the well-known eosinophil activator C5a. The range of efficacy of the CC chemokines compared to C5a in the activation of the respiratory burst was eotaxin = C5a > MCP-3 > RANTES. Production of reactive oxygen species was inhibited by pertussis toxin, staurosporin, genestein and wortmannin. Furthermore, eotaxin induced transient increases in intracellular calcium concentration ([Ca2+]i) in human eosinophils. Therefore, pertussis toxin-sensitive Gi-proteins, protein kinase C, tyrosine kinase, phosphatidylinositol-3-kinase and transient increases in [Ca2+]i are involved in the signal transduction of eosinophils following stimulation with eotaxin. In summary, this study reveals the importance of the CC chemokine eotaxin as a potent activator of the respiratory burst, actin polymerization and chemotaxis. Eotaxin, therefore, plays an important role not only by attracting eosinophils to the site of inflammation but also by damaging tissue by its capacity to induce the release of reactive oxygen species.
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PMID:Human eotaxin represents a potent activator of the respiratory burst of human eosinophils. 876 40

Eotaxin is a potent chemoattractant for eosinophils during inflammation and allergic reactions in the adult, but its role during development has not been studied. We report that eotaxin and its receptor, CCR-3, are expressed by embryonic tissues responsible for blood development, including the yolk sac, fetal liver, and fetal blood. We also found that eotaxin acts synergistically with stem cell factor (SCF) to accelerate the differentiation of embryonic mast cell progenitors and to promote the growth of Mac-1+/Gr-1- cells from progenitors isolated at 10-12 days of gestation. This response is diminished by Pertussis toxin, the Gi alpha inhibitor. These studies suggest that eotaxin is involved in the growth of myeloid cell progenitors and the differentiation of mast cells during embryogenic development.
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PMID:Eotaxin influences the development of embryonic hematopoietic progenitors in the mouse. 936 21

CC chemokines produced by CD8(+) T cells are known to act as HIV-suppressive factors. We studied the possible role of these chemokines in HIV-1-specific killing of target cells. We found that the activity of cytotoxic T lymphocytes (CTLs) in CTL lines or freshly isolated peripheral blood mononuclear cells from HIV-1-infected individuals is markedly enhanced by RANTES (regulated on activation, normal T cell expressed and secreted) and virtually abolished by an antibody neutralizing RANTES or the RANTES receptor antagonist RANTES(9-68). Lysis was mediated by CD8(+) major histocompatibility complex class I-restricted T cells and was obtained with target cells expressing epitopes of the HIV-1LAI proteins Gag, Pol, Env, and Nef. The cytolytic activity observed in the presence or absence of added RANTES could be abolished by pretreatment of the CTLs with pertussis toxin, indicating that the effect is mediated by a G protein-coupled receptor. The chemokines monocyte chemotactic protein (MCP)-3, MCP-4, and eotaxin acted like RANTES, whereas macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MCP-1, and stromal cell-derived factor 1 were inactive, suggesting a role for the eotaxin receptor, CCR3, and ruling out the involvement of CCR1, CCR2, CCR5, and CXCR4. CTL activity was abrogated by an antibody that blocks CCR3, further indicating that specific lysis is triggered via this chemokine receptor. These observations reveal a novel mechanism for the induction of HIV-1-specific cytotoxicity that depends on RANTES acting via CCR3.
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PMID:HIV-specific T cell cytotoxicity mediated by RANTES via the chemokine receptor CCR3. 968 38

Eosinophils play an important role in allergic and autoimmune diseases. They are activated by distinct chemokines, leading to the immigration into the inflamed tissue, and mediate tissue damage by releasing reactive oxygen species. Recently, eotaxin was found to have the broadest spectrum of activities of all eosinophil-activating CC chemokines. In this study we investigated the effect of the novel CC chemokine, eotaxin-2, on eosinophil effector functions and compared its activity with eotaxin. Using nitrobenzoxadiazole-phallacidin staining and flow cytometry, we show that eotaxin-2 induced rapid and transient actin polymerization, a prerequisite for cell migration and modulation of the respiratory burst, in eosinophils in the same range of efficacy as observed for eotaxin. Eotaxin-2 induced the release of reactive oxygen species in a dose-dependent manner; half maximal and maximal release were found at 50 ng/ml and 500 ng/ml, respectively. Surprisingly, the efficacy of eotaxin-2 was comparable to that of eotaxin and C5a. Release of reactive oxygen species was inhibited by pertussis toxin, indicating the involvement of Gi proteins in the signaling of eotaxin-2. Moreover, the anti-CC chemokine receptor 3 (CCR3) monoclonal antibody, 7B11, was able to inhibit transient rise in the cytosolic Ca2+ concentration and the release of reactive oxygen species following stimulation with eotaxin-2. Therefore, eotaxin-2 represents a potent CC chemokine for human eosinophils activating chemotaxis-related events, such as actin polymerization, and the respiratory burst via the CCR3. Moreover, the efficacy of eotaxin-2 seems to be in the same range as that of eotaxin which might re-evaluate the recent profile of activity of CC chemokines in the activation of human eosinophils.
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PMID:Eotaxin-2 activates chemotaxis-related events and release of reactive oxygen species via pertussis toxin-sensitive G proteins in human eosinophils. 969 84

Eotaxin is a potent chemoattractant for eosinophils during inflammation and allergic reactions in the adult, but its role in the embryonic development of the hematopoietic system has not been examined. We report here that eotaxin and its receptor, CCR-3, are expressed by embryonic tissues responsible for blood development, such as fetal liver (FL), yolk sac (YS), and peripheral blood. We found that eotaxin acts synergistically with stem cell factor to accelerate the differentiation of embryonic mast cell progenitors, and this response can be suppressed by pertussis toxin, an inhibitor of chemokine-induced signaling through Gialpha protein and chemotaxis. Eotaxin promotes the differentiation of fetal mast cell progenitors into differentiated mast cells as defined by the expression of mast cell specific proteases. Furthermore, in combination with stem cell factor (SCF), it promotes the growth of Mac-1(+) myeloid cells from embryonic progenitors. These studies suggest that eotaxin may be involved in the growth of granulocytic progenitors and the differentiation and/or function of mast cells during embryogenesis and/or pathological conditions that induce high levels of eotaxin, such as allergic responses.
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PMID:Eotaxin modulates myelopoiesis and mast cell development from embryonic hematopoietic progenitors. 973 Oct 45

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL24-51) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines. Both monocyte migration and Ca2+ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of beta-chemokines from the beta-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL24-51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic beta-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.
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PMID:HIV-1 Tat protein mimicry of chemokines. 978 57

CC chemokine receptor-3 (CCR-3) is a major receptor involved in regulating eosinophil trafficking; therefore, elucidation of ligand-induced CCR-3 events has important implications in understanding the biological and pathological properties of eosinophils. Previous studies have demonstrated that unique receptor events occur in different cell types supporting investigation of CCR-3-mediated events in eosinophilic cells. We now report biochemical characterization of CCR-3 internalization following exposure of eosinophils to CCR-3 ligands. Treatment of freshly isolated human eosinophils with CCR-3 ligands resulted in marked and differential internalization of CCR-3 in a dose-dependent manner. Exposure to 100 ng/ml eotaxin reduced surface expression to 43, 43, and 76% at 15 min, 1 h, and 3 h, respectively. RANTES (reduced on activation T cell expressed and secreted) treatment induced more significant and prolonged internalization of CCR-3 than eotaxin; following 100 ng/ml of RANTES, 29, 24, and 47% of the receptor was expressed at 15 min, 3 h, and 18 h, respectively. Confocal microscopy demonstrated that receptor modulation involved receptor internalization by an endocytic pathway shared with the transferrin receptor. Receptor internalization was accompanied by partial degradation of CCR-3, and reexpression of CCR-3 was dependent in part upon de novo protein synthesis. Internalization was not blocked by pretreatment of eosinophils with pertussis toxin. Furthermore, staurosporine did not inhibit internalization although it blocked phorbol 12-myristate 13-acetate-induced CCR-3 down-modulation. These results demonstrate that CCR-3 ligands induce differential receptor internalization that is not dependent upon Gi-protein coupling, calcium transients, or protein kinase C.
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PMID:CC chemokine receptor-3 undergoes prolonged ligand-induced internalization. 1021 40

CCR-3 is a major receptor involved in regulating eosinophil trafficking. Initial analysis of chemokine receptors has demonstrated unique receptor events in different cell types, indicating the importance of investigating CCR-3 events in eosinophilic cell lines. We now report that the eosinophilic cell line, acute myelogenous leukemia (AML) 14.3D10, expresses eosinophil granule proteins and eotaxin, but has no detectable expression of eosinophil chemokine receptors. Treatment of the cell line with butyric acid and IL-5 results in a dose-dependent synergistic induction of CCR-3 and, to a lesser extent, CCR-1 and CCR-5. Interestingly, using a luciferase reporter construct under the control of the hCCR-3 promoter, the uninduced and induced cells display high, but comparable, levels of promoter activity. Differentiated AML cells developed enhanced functional activation, as indicated by adhesion to respiratory epithelial cells and chemokine-induced transepithelial migration. Chemokine signaling did not inhibit adenylate cyclase activity even though calcium transients were blocked by pertussis toxin. Additionally, chemokine-induced calcium transients were inhibited by pretreatment with PMA, but not forskolin. Eotaxin treatment of differentiated AML cells resulted in marked down-modulation of CCR-3 expression for at least 18 h. Receptor internalization was not dependent upon chronic ligand exposure and was not accompanied by receptor degradation. Thus, CCR-3 is a late differentiation marker on AML cells and uses a signal transduction pathway involving rapid and prolonged receptor internalization, calcium transients inhibitable by protein kinase C but not protein kinase A, and the paradoxical lack of inhibition of adenylate cyclase activity.
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PMID:Molecular analysis of CCR-3 events in eosinophilic cells. 1062 56

Eosinophils are major effector cells in cellular inflammatory conditions such as parasitic infections, atopic diseases, bullous dermatoses, and vasculitis. Biological activities of adenosine triphosphate (ATP) were characterized in human eosinophils and compared with those of other eosinophil activators such as complement fragment product C5a, platelet-activating factor (PAF), and eotaxin. ATP initiated production of reactive oxygen metabolites, as demonstrated by lucigenin-dependent chemiluminescence. Furthermore, ATP caused up-regulation of the integrin CD11b. In addition, fluorescence microscope measurements labeled with fura-2 (1-[2-(5-carboxy-oxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2' -amino-5' -methyl-phenoxy)-ethane-N, N, N, N'-tetraacetic acid, pentaacetoxymethyl ester) eosinophils in the presence or absence of ethyleneglycotetraacetic acid (EGTA) indicated that there was Ca(++) mobilization from intracellular stores by ATP. Flow cytometric studies showed transient actin polymerization upon stimulation with ATP and its stable analogues adenosine 5'-0-(3-thiotriphosphate) and 2-methylthioadenosine triphosphate tetrasodium (met-ATP). The reactions induced by ATP were comparable to those obtained by C5a, PAF, and eotaxin. Production of reactive oxygen metabolites and actin polymerization after stimulation with ATP was inhibited by pertussis toxin, which indicated involvement of receptor-coupled guanine nucleotide-binding proteins (G(i) proteins). In addition, experiments with oxidized ATP also suggest involvement of P2X receptors in this activation process. The results show that ATP is a strong activator of eosinophils and has biological activity comparable to those of the eosinophil chemotaxins C5a, PAF, and eotaxin. The findings strongly suggest a role of ATP in the pathogenesis of eosinophilic inflammation as an activator of proinflammatory effector functions.
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PMID:Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation: Ca(++) mobilization and actin reorganization in human eosinophils. 1064 11

Chemokine-induced eosinophil chemotaxis is mediated primarily through the C-C chemokine receptor, CCR3. We have now detected CCR3 immunoreactivity on epithelial cells in biopsies of patients with asthma and other respiratory diseases. CCR3 mRNA was detected by Northern blot analysis after TNF-alpha stimulation of the human primary bronchial epithelial cells as well as the epithelial cell line, BEAS-2B; IFN-gamma potentiated the TNF-alpha-induced expression. Western blots and flow cytometry confirmed the expression of CCR3 protein. This receptor is functional based on studies demonstrating eotaxin-induced intracellular Ca(2+) flux and tyrosine phosphorylation of cellular proteins. The specificity of this functional response was confirmed by blocking these signaling events with anti-CCR3 mAb (7B11) or pertussis toxin. Furthermore, (125)I-eotaxin binding assay confirmed that CCR3 expressed on epithelial cells have the expected ligand specificity. These studies indicate that airway epithelial cells express CCR3 and suggest that CCR3 ligands may influence epithelial cell functions.
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PMID:Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells. 1116 Jan 84


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