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)

The present study was aimed at defining the chemotactic activity of phosphatidic acid, which is rapidly produced by phagocytes in response to chemotactic agonists. Exogenously added phosphatidic acid induced human monocyte directional migration across polycarbonate filters with an efficacy (number of cell migrated) comparable to that of "classical" chemotactic factors. In lipid specificity studies, activity of phosphatidic acid decreased with increasing acyl chain length but was restored by introducing unsaturation in the acyl chain with the most active form being the natural occurring 18:0,20:4-phosphatidic acid. Lysophosphatidic acid was also active in inducing monocyte migration. No other phospholipid and lysophospholipid tested was effective in this response. Monocyte migration was regulated by a gradient of phosphatidic acid and lysophosphatidic acid bound to the polycarbonate filter, in the absence of detectable soluble chemoattractant. Migration was also observed if phospholipids were bound to fibronectin-coated polycarbonate filters. Thus, phosphatidic acid and lysophosphatidic acid, similarly to other physiological chemoattractants (e.g. C5a and interleukin-8), induce cell migration by an haptotactic mechanism. Phosphatidic acid caused a rapid increase of filamentous actin and, at higher concentrations, induced a rise of intracellular calcium concentration. Monocyte migration to phosphatidic acid and lysophosphatidic acid, but not to diacylglycerol, was inhibited in a concentration-dependent manner by Bordetella pertussis toxin, while cholera toxin was ineffective. In the chemotactic assay, phosphatidic acid and lysophosphatidic acid induced a complete homologous desensitization and only partially cross-desensitized one with each other, or with diacyl-glycerol and monocyte chemotactic protein-1. Suramine inhibited monocyte chemotaxis with a different efficiency phosphatidic acid > lysophosphatidic acid" diacyl-glycerol On the contrary, monocyte chemotactic protein-1-induced chemotaxis was not affected by the drug. Collectively, these data show that phosphatidic acid induces haptotactic migration of monocytes that is at least in part receptor-mediated. These results support a role for phosphatidic acid and lysophosphatidic acid in the regulation of leukocyte accumulation into tissues.
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PMID:Phosphatidic acid and lysophosphatidic acid induce haptotactic migration of human monocytes. 759 25

The increase in intracellular free Ca2+ ([Ca2+]i) associated with interaction of monocyte chemotactic protein-1 (MCP-1) and related chemokines beta with adherent human blood monocytes was investigated at the single-cell level. We used f-MLP as reference chemotactic agent. MCP-1 caused an increase in [Ca2+]i in individual adherent monocytes, with 95% of cells responding to the chemokine at 20 ng/mL. Response to MCP-1 was already detectable at 1 pg/mL, whereas at least 5 ng/mL were required for significant chemotactic response. The kinetics of the increase in [Ca2+]i were considerably different for MCP-1 compared with f-MLP. MCP-1 produced a slow increase of [Ca2+]i that reached a plateau in 5 to 7 minutes. On the other hand, the increase of [Ca2+]i induced by f-MLP appeared to be biphasic, with a fast phase peaking after 5 to 40 seconds followed by a slower wave. Blocking of Ca2+ channels by Ni2+ or Cd2+ and/or chelation of extracellular free Ca2+ considerably reduced but did not abolish response to MCP-1, had no effect on the first wave of [Ca2+]i induced by f-MLP, and completely abrogated the second, slower wave. Thapsigargin, which empties intracellular Ca2+ stores, inhibited f-MLP-induced [Ca2+]i increase but fully blocked the action of MCP-1 only when combined with Ni2+. Thus, increase of [Ca2+]i induced by MCP-1 is apparently due to independent opening of a channel and mobilization from intracellular stores, whereas f-MLP-induced mobilization of Ca2+ from stores causes subsequent opening of a channel. At variance with MCP-1, the related chemokine MCP-2 induced only a low increase of [Ca2+]i in about 40% of adherent monocytes. Inhibition of chemokine-induced increase of [Ca2+]i by cholera or pertussis toxin indicated that MCP-1 and MCP-2 activate monocytes through different intracellular pathways. These results demonstrate at the single-cell level that the mechanisms and dynamics of increased [Ca2+]i are considerably different for f-MLP and chemokines beta. In addition, the [Ca2+]i increase induced by the two related chemokines beta MCP-1 and MCP-2 appears to be differently regulated, suggesting interaction with distinct receptors.
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PMID:Single-cell analysis of macrophage chemotactic protein-1-regulated cytosolic Ca2+ increase in human adherent monocytes. 766 86

Chemotactic cytokines related to interleukin-8 (IL-8; CXC-chemokines) or monocyte chemotactic protein-1 (MCP-1; CC-chemokines) have been shown to stimulate human basophils, and are considered important tissue-derived mediators of inflammation. We have studied the effects of four CC-chemokines and show that MCP-1, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent basophil agonists inducing a rapid change of cytosolic free calcium ([Ca2+]i), the release of histamine and sulfido-leukotrienes, and chemotaxis. MCP-1 was the most potent stimulus of release, and the only chemokine that induced marked exocytosis in basophils without pretreatment with interleukin-3. RANTES was the strongest stimulus of chemotaxis, but only a moderate stimulus of release. MIP-1 alpha elicited relatively weak chemotaxis and release responses, but was effective at considerably lower concentrations than MCP-1 and RANTES. MIP-1 beta, by contrast, despite its high homology to MIP-1 alpha, was totally inactive. Normodense human eosinophils, tested for comparison, responded in a similar fashion to RANTES and MIP-1 alpha, but were unresponsive to MCP-1 and MIP-1 beta. All CC-chemokines except MIP-1 beta induced a similar rapid and transient rise of [Ca2+]i that was sensitive to pertussis toxin, indicating that they activate basophils via G-protein-coupled receptors. Cross-desensensitization experiments indicate that basophils bear different CC-chemokine receptors. Some interact selectively with MCP-1 or RANTES, while others are shared by RANTES and MIP-1 alpha.
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PMID:RANTES and related chemokines activate human basophil granulocytes through different G protein-coupled receptors. 768 Jun 15

Under certain physiological and pathological conditions, natural killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active--though less potent--attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
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PMID:Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3. 780 52

We have previously shown that minimally oxidized LDL (MM-LDL) activated endothelial cells to increase their interaction with monocytes but not neutrophils, inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor (M-CSF). In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced. Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells. A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above. Incubation of endothelial cells with MM-LDL caused a 173% increase in intracellular cAMP levels. Agents which increased cAMP levels, including cholera toxin, pertussis toxin, dibutyryl cAMP, and isoproterenol mimicked the actions of MM-LDL. Agents which elevated cAMP were also shown to activate NF kappa B, suggesting a role for this transcription factor in activation of monocyte-endothelial interactions. Although endothelial leukocyte adhesion molecule (ELAM) mRNA synthesis can be regulated by NF kappa B, ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL. We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels.
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PMID:Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. 839 92

Members of the C-C family of chemotactic cytokines promote chemotaxis and adhesion of leukocytes. In this study, we have identified a murine T cell hybrid that expresses receptors to the chemotactic cytokine monocyte chemotactic protein-1 (MCP-1). This cell line was used to examine MCP-1 receptor-mediated signal transduction events in a homologous system in the absence of interference with other receptors. Our results show that in the 3B4 M1.9 T cell hybrid, MCP-1 receptors mediate intracellular calcium mobilization and extracellular calcium import without detectable increases in total water-soluble inositol phosphates. In addition, MCP-1 regulates the tyrosine phosphorylation of specific substrates at 42 and 44 kDa and induces mobility shift of p42/44 mitogen-activated protein kinases. MCP-1-mediated calcium responses, tyrosine phosphorylation, and the electrophoretic mobility shift of p42/44 mitogen-activated protein kinases can be inhibited by pretreatment of cells with pertussis toxin, indicating a role for Gi-like G proteins in coupling the MCP-1R to signal transduction.
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PMID:Early signal transduction by the receptor to the chemokine monocyte chemotactic protein-1 in a murine T cell hybrid. 856 34

We have previously reported that cytokines such as IL-9, IL-4, and IL-6 protect murine thymic lymphoma cell lines against dexamethasone-induced apoptosis. A similar activity, which could not be ascribed to any of these factors, was found in a number of human T cell supernatants that enabled mouse BW5147 thymic lymphoma not only to escape apoptosis but also to maintain proliferation. The protein responsible for this activity was purified to homogeneity from the culture medium of activated leukemic T cells and was found to be identical with the I-309 chemokine. Half-maximal anti-apoptotic activity was obtained with approximately 1 ng/ml, a concentration considerably lower than that required for the monocyte chemotactic activity of this molecule, as measured on THP-1 cells. The purified I-309 also improved the survival of two other mouse thymic lymphoma cell lines. This activity was as potent as that of IL-9, which was the strongest anti-apoptotic factor found to date for these cells. Similar results were obtained for BW5147 cells with recombinant I-309 and with T cell activation gene-3, the murine homologue of I-309, but not with other members of the chemokine family, including IL-8, neutrophil-activating peptide-2, granulocyte chemotactic protein-2, macrophage inflammatory protein-1a, RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), and MCP-2. MCP-3, however, showed a minor, but significant effect in this model. Unlike that of IL-9, the activity of I-309 was completely inhibited in the presence of pertussis toxin, indicating the involvement of a G protein in this process.
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PMID:I-309/T cell activation gene-3 chemokine protects murine T cell lymphomas against dexamethasone-induced apoptosis. 880 59

The newly described products of 5-hydroxyeicosanoid dehydrogenase, 5-oxo-6,8,11,14-eicosatetraenoic acid (ETE) and 5-oxo-15(OH)ETE, induced directional migration and actin polymerization of human monocytes in vitro. At peak concentrations, the two eicosanoids had a chemotactic activity of about 40% of that observed in the presence of an optimal concentration of FMLP and twice the activity elicited by the related eicosanoid 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE). 15-Oxo-ETE showed a very low but detectable chemotactic activity. All of these chemotactic responses were blocked by Bordetella pertussis toxin, but were resistant to LY255283, a leukotriene B4 (LTB4) receptor antagonist. 5-Oxo-ETEs and 5-HETE induced homologous desensitization of chemotactic response, but did not cross-desensitize to other chemotactic agonists (e.g., monocyte chemotactic protein (MCP)-1 and LTB4). 5-Oxo-ETEs increased in a synergistic fashion the monocyte migration to MCP-1 and MCP-3. In the same range of concentrations, 5-oxo-ETE increased MCP-1-induced release of arachidonic acid from labeled monocytes. No synergistic interaction was observed when FMLP was used as chemoattractant. Thus, this study identifies monocytes as cells responsive to 5-oxo-ETEs and shows that monocyte activation by 5-oxo-ETEs occurs through an LTB4 receptor-independent mechanism that associates with pertussis toxin-sensitive G proteins. The synergistic interaction between 5-oxo-ETEs and C-C chemokines, two families of mediators both synthesized by phagocytic cells, may be relevant in vivo for the regulation of monocyte accumulation at sites of allergic and inflammatory reactions.
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PMID:Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3. 890 47

The factors that control migration of mast cells to sites of inflammation and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of murine mast cells, only stem cell factor (SCF) is known to induce migration of human mast cells. We report here that the anaphylatoxins C3a and C5a are chemotactic factors for the human mast cell line HMC-1, human cord blood-derived mast cells (CBMC) and cutaneous mast cells in vitro. The presence of an extracellular matrix protein, laminin, was required for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 microg/mL (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration of HMC-1 cells, indicating that Gi proteins are involved in complement-activated signal transduction pathways in human mast cells. Both C3a and C5a also induced a rapid and transient mobilization of intracellular free calcium ([Ca2+]i) in HMC-1 cells. Besides SCF, other chemotactic factors tested, such as interleukin-3, nerve growth factor, transforming growth factor beta, RANTES (regulated upon activation, normal Tcell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.
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PMID:C3a and C5a stimulate chemotaxis of human mast cells. 910 6

The novel human CC-chemokine monocyte chemotactic protein-4 (MCP-4) is a chemotaxin for eosinophils. Here, the biological activities and the activation profile of MCP-4 was further characterized in eosinophils and compared to other activators such as platelet activating factor (PAF), Eotaxin and RANTES. As demonstrated by lucigenin-dependent chemiluminescence and superoxide dismutase-inhibitable cytochrome C reduction MCP-4 stimulated the production of reactive oxygen metabolites. Furthermore, MCP-4 induced up-regulation of the integrin CD11b. Flow cytometric studies revealed rapid and transient actin polymerization upon stimulation with MCP-4. At optimal concentrations the changes induced by MCP-4 were weaker than the effects after stimulation with PAF and comparable to those obtained by RANTES and Eotaxin. Cell responses elicited by MCP-4 were inhibited by pertussis toxin indicating involvement of Gi-proteins in this signal pathway. These findings point to a role of MCP-4 in the pathogenesis of eosinophilic inflammation as chemotaxin as well as activator of pro-inflammatory effector functions.
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PMID:The monocyte chemotactic protein-4 induces oxygen radical production, actin reorganization, and CD11b up-regulation via a pertussis toxin-sensitive G-protein in human eosinophils. 936 76


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