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Fernando Q. Cunha - One of the best experts on this subject based on the ideXlab platform.
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NDP-MSH inhibits Neutrophil Migration through nicotinic and adrenergic receptors in experimental peritonitis.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Jozi G. Figueiredo, Fernando Q. Cunha, Sergio H Ferreira, Thiago M. Cunha, Ana Elisa Ferreira, Rangel L. Silva, Luis Ulloa, Paolo Grieco, Alexandre KanashiroAbstract:Melanocortin is a potent anti-inflammatory molecule. However, little is known about the effect of melanocortin on acute inflammatory processes such as Neutrophil Migration. In the present study, we investigated the ability of [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH), a semisynthetic melanocortin compound, in the inhibition of Neutrophil Migration in carrageenin-induced peritonitis model. Herein, subcutaneous pretreatment with NDP-MSH decreased Neutrophil trafficking in the peritoneal cavity in a dose-dependent manner. NDP-MSH inhibited vascular leakage, leukocyte rolling, and adhesion and reduced peritoneal macrophage inflammatory protein 2, but not TNF-alpha, IL-1beta, IL-10, and keratinocyte-derived chemokine production. In addition, the effect on Neutrophil Migration was reverted by the pretreatment with both propranolol (a nonselective beta-adrenergic antagonist) and mecamylamine (a nonselective nicotinic antagonist) but not by splenectomy surgery. Moreover, NDP-MSH intracerebroventricular administration inhibited Neutrophil Migration, indicating participation of the central nervous system. Our results propose that the NDP-MSH effect may be due to a spleen-independent neuro-immune pathway that efficiently regulates excessive Neutrophil recruitment to tissues.
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regulation of chemokine receptor by toll like receptor 2 is critical to Neutrophil Migration and resistance to polymicrobial sepsis
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Jose C Alvesfilho, Sergio H Ferreira, João S. Silva, Fernando Spiller, Fabricio O. Souto, Andressa De Freitas, Heitor A Paulaneto, Ricardo T Gazzinelli, Mauro M Teixeira, Fernando Q. CunhaAbstract:Patients with sepsis have a marked defect in Neutrophil Migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of Neutrophil Migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating Neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired Migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of Neutrophil Migration. Moreover, TLR2−/− mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the Neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, Neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein–coupled receptor kinases 2 (GRK2) in Neutrophils; increased expression of GRK2 was seen in blood Neutrophils from WT mice, but not TLR2−/− mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.
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acute phase protein α 1 acid glycoprotein mediates Neutrophil Migration failure in sepsis by a nitric oxide dependent mechanism
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Fabiola L Mestriner, Helen Julie Laure, S H Ferreira, Fernando Spiller, Fabricio O. Souto, José César Rosa, Beatriz Martins Tavaresmurta, Anibal Basilefilho, Lewis J Greene, Fernando Q. CunhaAbstract:The reduction of circulating Neutrophil Migration to infection sites is associated with a poor outcome of severe sepsis. α-1-Acid glycoprotein (AGP) was isolated from the sera of severely septic patients by HPLC and acrylamide gel electrophoresis and identified by mass spectrometry. Both the isolated protein and commercial AGP inhibited carrageenin-induced Neutrophil Migration into the rat peritoneal cavity when administered i.v. at a dose of 4.0 μg per rat (95 pmol per rat). Analysis by intravital microscopy demonstrated that both proteins inhibited the rolling and adhesion of leukocytes in the mesenteric microcirculation. The inhibitory activity was blocked by 50 mg/kg aminoguanidine, s.c., and was not demonstrable in inducible nitric oxide synthase (iNOS) knockout mice. Incubation of AGP with Neutrophils from healthy subjects induced the production of NO and inhibited the Neutrophil chemotaxis by an iNOS/NO/cyclic guanosine 3,5-monophosphate-dependent pathway. In addition, AGP induced the l-selectin shedding by Neutrophils. The administration of AGP to rats with mild cecal ligation puncture sepsis inhibited Neutrophil Migration and reduced 7-day survival from ≈80% to 20%. These data demonstrate that AGP, an acute-phase protein, inhibits Neutrophil Migration by an NO-dependent process and suggest that AGP also participates in human sepsis.
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Toll-like receptor 4 signaling leads to Neutrophil Migration impairment in polymicrobial sepsis.
Critical Care Medicine, 2006Co-Authors: José C. Alves-filho, Andressa De Freitas, Momtchilo Russo, Fernando Q. CunhaAbstract:Objective We have documented an impaired Neutrophil Migration toward the infectious focus in severe sepsis. This phenomenon appears to be mediated by nitric oxide, the release of which is stimulated by circulating inflammatory cytokines released by immune cells after stimulation by bacteria and/or their products. Toll-like receptor 4 (TLR4) is the major recognition receptor for lipopolysaccharide, a component of Gram-negative bacterial cell walls. In the present study, we investigated whether TLR4 is involved in the failure of Neutrophil Migration in mice subjected to polymicrobial or Gram-negative sepsis. Design Controlled animal study. Setting University research laboratory. Subjects Male C3H/HeJ (TLR4-deficient) and C3H/HePas (TLR4-normal) mice. Interventions Mice were subjected to sublethal or lethal polymicrobial sepsis, both induced by cecal ligation and puncture or intraperitoneal polymicrobial inoculation, and subjected to sublethal Gram-negative sepsis induced by intraperitoneal Salmonella typhimurium inoculation (GNI). Survival was monitored for 5 days. In separate experiments, mice were killed 6 hrs after sepsis induction, and intraperitoneal Neutrophil Migration, bacteremia, lung Neutrophil sequestration, and levels of cytokines, chemokines, and nitrate were evaluated. Measurements and results TLR4-deficient (C3H/HeJ) mice presented incapacity to promote Neutrophil recruitment to the infectious site after sublethal GNI, resulting in high mortality. However, TLR4 signaling is not essential to display Neutrophil Migration in sublethal polymicrobial sepsis induced by both cecal ligation and puncture and polymicrobial inoculation models, but surprisingly, it is crucial to establish the impairment of Neutrophil Migration in lethal polymicrobial sepsis, since TLR4-deficient mice that underwent lethal cecal ligation and puncture or polymicrobial inoculation did not present failure of Neutrophil Migration to infectious focus. As a consequence, these animals presented low bacteremia and a high survival rate and did not display systemic inflammation, determined by high levels of circulating cytokines and lung Neutrophil sequestration and chemokine production. Conclusion These results highlight the harmful role of TLR4 signaling in polymicrobial severe sepsis.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on Neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil Migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce Neutrophil Migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that Neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.
Sergio H Ferreira - One of the best experts on this subject based on the ideXlab platform.
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NDP-MSH inhibits Neutrophil Migration through nicotinic and adrenergic receptors in experimental peritonitis.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Jozi G. Figueiredo, Fernando Q. Cunha, Sergio H Ferreira, Thiago M. Cunha, Ana Elisa Ferreira, Rangel L. Silva, Luis Ulloa, Paolo Grieco, Alexandre KanashiroAbstract:Melanocortin is a potent anti-inflammatory molecule. However, little is known about the effect of melanocortin on acute inflammatory processes such as Neutrophil Migration. In the present study, we investigated the ability of [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH), a semisynthetic melanocortin compound, in the inhibition of Neutrophil Migration in carrageenin-induced peritonitis model. Herein, subcutaneous pretreatment with NDP-MSH decreased Neutrophil trafficking in the peritoneal cavity in a dose-dependent manner. NDP-MSH inhibited vascular leakage, leukocyte rolling, and adhesion and reduced peritoneal macrophage inflammatory protein 2, but not TNF-alpha, IL-1beta, IL-10, and keratinocyte-derived chemokine production. In addition, the effect on Neutrophil Migration was reverted by the pretreatment with both propranolol (a nonselective beta-adrenergic antagonist) and mecamylamine (a nonselective nicotinic antagonist) but not by splenectomy surgery. Moreover, NDP-MSH intracerebroventricular administration inhibited Neutrophil Migration, indicating participation of the central nervous system. Our results propose that the NDP-MSH effect may be due to a spleen-independent neuro-immune pathway that efficiently regulates excessive Neutrophil recruitment to tissues.
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inhibition of Neutrophil Migration by hemopexin leads to increased mortality due to sepsis in mice
American Journal of Respiratory and Critical Care Medicine, 2011Co-Authors: Fernando Spiller, Helen Julie Laure, Fabiola L Mestriner, Fabricio O. Souto, Andressa De Freitas, José César Rosa, Carlotta Costa, Francesca Vinchi, Jose C Alvesfilho, Sergio H FerreiraAbstract:Rationale: The reduction of Neutrophil Migration to the bacterial focus is associated with poor outcome in sepsis.Objectives: The objective of this study was to identify soluble substances in the blood of septic mice that inhibit Neutrophil Migration.Methods: A pool of serum obtained from mice 2 hours after the induction of severe sepsis by cecal ligation and puncture inhibited the Neutrophil Migration. The proteins with inhibitory activity on Neutrophil Migration were isolated by Blue-Sepharose chromatography, high-performance liquid chromatography, and electrophoresis, and identified by mass spectrometry.Measurements and Main Results: Hemopexin was identified as the serum component responsible for the inhibition of Neutrophil Migration. In sepsis, the pretreatment of wild-type mice with hemopexin inhibited Neutrophil Migration to the focus of infection and decreased the survival rate from 87.5 to 50.0%. Hemopexin-null mice subjected to severe sepsis presented normal Neutrophil Migration, low bacteremia,...
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prostaglandin mediates il 23 il 17 induced Neutrophil Migration in inflammation by inhibiting il 12 and ifnγ production
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Henrique Lemos, Sergio H Ferreira, Fabricio O. Souto, Waldiceu A. Verri, Thiago M. Cunha, Iain B. Mcinnes, Silvio M. Vieira, Renata Grespan, Karla Fernandes, Foo Y. LiewAbstract:IL-23/IL-17-induced Neutrophil recruitment plays a pivotal role in rheumatoid arthritis (RA). However, the mechanism of the Neutrophil recruitment is obscure. Here we report that prostaglandin enhances the IL-23/IL-17-induced Neutrophil Migration in a murine model of RA by inhibiting IL-12 and IFN γ production. Methylated BSA (mBSA) and IL-23-induced Neutrophil Migration was inhibited by anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFNγ but was enhanced by prostaglandin E2 (PGE2). IL-23-induced IL-17 production was increased by PGE2 and suppressed by COX-inhibition or IL-12. Furthermore, COX inhibition failed to reduce IL-23-induced Neutrophil Migration in IL-12- or IFNγ-deficient mice. IL-17-induced Neutrophil Migration was not affected by COX inhibitors, IL-12, or IFNγ but was inhibited by MK886 (a leukotriene synthesis inhibitor), anti-TNFα, anti-CXCL1, and anti-CXCL5 antibodies and by repertaxin (a CXCR1/2 antagonist). These treatments all inhibited mBSA- or IL-23-induced Neutrophil Migration. IL-17 induced Neutrophil chemotaxis through a CXC chemokines-dependent pathway. Our results suggest that prostaglandin plays an important role in IL-23-induced Neutrophil Migration in arthritis by enhancing IL-17 synthesis and by inhibiting IL-12 and IFNγ production. We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs.
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regulation of chemokine receptor by toll like receptor 2 is critical to Neutrophil Migration and resistance to polymicrobial sepsis
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Jose C Alvesfilho, Sergio H Ferreira, João S. Silva, Fernando Spiller, Fabricio O. Souto, Andressa De Freitas, Heitor A Paulaneto, Ricardo T Gazzinelli, Mauro M Teixeira, Fernando Q. CunhaAbstract:Patients with sepsis have a marked defect in Neutrophil Migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of Neutrophil Migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating Neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired Migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of Neutrophil Migration. Moreover, TLR2−/− mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the Neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, Neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein–coupled receptor kinases 2 (GRK2) in Neutrophils; increased expression of GRK2 was seen in blood Neutrophils from WT mice, but not TLR2−/− mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.
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peroxisome proliferator activated receptor γ ligand 15 deoxy δ12 14 prostaglandin j2 reduces Neutrophil Migration via a nitric oxide pathway
Journal of Immunology, 2008Co-Authors: Marcelo Henrique Napimoga, Fabiola L Mestriner, Fabricio O. Souto, Andressa De Freitas, Jose C Alvesfilho, Silvio M. Vieira, Renata Grespan, Daniela Dalsecco, Toshihisa Kawai, Sergio H FerreiraAbstract:Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such as 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) have been implicated as a new class of anti-inflammatory compounds with possible clinical applications. Based on this concept, this investigation was designed to determine the effect of 15d-PGJ2-mediated activation of PPAR-gamma ligand on Neutrophil Migration after an inflammatory stimulus and clarify the underlying molecular mechanisms using a mouse model of peritonitis. Our results demonstrated that 15d-PGJ2 administration decreases leukocyte rolling and adhesion to the inflamed mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ2-mediated suppression of Neutrophil Migration to the inflammatory site. Moreover, inducible NOS-/- mice were not susceptible to 15d-PGJ2-mediated suppression of Neutrophil Migration to the inflammatory sites when compared with their wild type. In addition, 15d-PGJ2-mediated suppression of Neutrophil Migration appeared to be independent of the production of cytokines and chemokines, since their production were not significantly affected in the carrageenan-injected peritoneal cavities. Finally, up-regulation of carrageenan-triggered ICAM-1 expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ2, whereas 15d-PGJ2 inhibited F-actin rearrangement process in Neutrophils. Taken together these findings demonstrated that 15d-PGJ2 suppresses inflammation-initiated Neutrophil Migration in a mechanism dependent on NO production in mesenteric tissues.
Claudio Canetti - One of the best experts on this subject based on the ideXlab platform.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on Neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil Migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce Neutrophil Migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that Neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on Neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil Migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce Neutrophil Migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that Neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory protein-1alpha (MIP-1alpha)[CC chemokine ligand 3 (CCL3)], MIP-1beta[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on Neutrophil Migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor alpha (TNF-alpha) and leukotriene B(4)(LTB(4)). Herein, we show increased mRNA expression for MIP-1alpha[CCL3], MIP-1beta[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA-challenged, immunized mice, as well as MIP-1alpha[CCL3] and RANTES[CCL5] but not MIP-1beta[CCL4] proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP-1alpha[CCL3](-/-) mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP-1beta[CCL4]. MIP-1alpha[CCL3] mediated Neutrophil Migration in immunized mice through induction of TNF-alpha and LTB(4) synthesis, as these mediators were detected in the exudates harvested from OVA-challenged immunized wild-type but not MIP-1alpha[CCL3](-/-) mice; administration of MIP-1alpha[CCL3] induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF-alpha antibody in TNF receptor 1 (p55(-/-))-deficient mice or by MK 886 (a 5-lipoxygenase inhibitor); and MIP-1alpha[CCL3] failed to induce LTB(4) production in p55(-/-) mice. MIP-1alpha[CCL3] used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1alpha[CCL3] failed to induce Neutrophil Migration in CCR1(-/-) mice, in contrast to CCR5(-/-) mice. In summary, we have demonstrated that Neutrophil Migration observed in this model of immune inflammation is mediated by MIP-1alpha[CCL3], which via CCR1, induces the sequential release of TNF-alpha and LTB(4). Therefore, whether a similar pathway mediates Neutrophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.
Janeusa T Souto - One of the best experts on this subject based on the ideXlab platform.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on Neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil Migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce Neutrophil Migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that Neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on Neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil Migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce Neutrophil Migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that Neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.
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mip 1α ccl3 acting on the ccr1 receptor mediates Neutrophil Migration in immune inflammation via sequential release of tnf α and ltb4
Journal of Leukocyte Biology, 2005Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. CunhaAbstract:In the present study, we investigated the involvement of macrophage-inflammatory protein-1alpha (MIP-1alpha)[CC chemokine ligand 3 (CCL3)], MIP-1beta[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on Neutrophil Migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)-triggered Neutrophil Migration in immunized mice depends on the sequential release of tumor necrosis factor alpha (TNF-alpha) and leukotriene B(4)(LTB(4)). Herein, we show increased mRNA expression for MIP-1alpha[CCL3], MIP-1beta[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA-challenged, immunized mice, as well as MIP-1alpha[CCL3] and RANTES[CCL5] but not MIP-1beta[CCL4] proteins in the peritoneal exudates. OVA-induced Neutrophil Migration response was muted in immunized MIP-1alpha[CCL3](-/-) mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP-1beta[CCL4]. MIP-1alpha[CCL3] mediated Neutrophil Migration in immunized mice through induction of TNF-alpha and LTB(4) synthesis, as these mediators were detected in the exudates harvested from OVA-challenged immunized wild-type but not MIP-1alpha[CCL3](-/-) mice; administration of MIP-1alpha[CCL3] induced a dose-dependent Neutrophil Migration, which was inhibited by treatment with an anti-TNF-alpha antibody in TNF receptor 1 (p55(-/-))-deficient mice or by MK 886 (a 5-lipoxygenase inhibitor); and MIP-1alpha[CCL3] failed to induce LTB(4) production in p55(-/-) mice. MIP-1alpha[CCL3] used CCR1 to promote Neutrophil recruitment, as OVA or MIP-1alpha[CCL3] failed to induce Neutrophil Migration in CCR1(-/-) mice, in contrast to CCR5(-/-) mice. In summary, we have demonstrated that Neutrophil Migration observed in this model of immune inflammation is mediated by MIP-1alpha[CCL3], which via CCR1, induces the sequential release of TNF-alpha and LTB(4). Therefore, whether a similar pathway mediates Neutrophil Migration in human immune-inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.
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In Vitro Neutrophil Migration Requires Protein Kinase C-Delta (δ-PKC)-Mediated Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Phosphorylation
Inflammation, 2015Co-Authors: Mary K. Sheats, Kenneth B Adler, Eui Jae Sung, Samuel L. JonesAbstract:Dysregulated release of Neutrophil reactive oxygen species and proteolytic enzymes contributes to both acute and chronic inflammatory diseases. Therefore, molecular regulators of these processes are potential targets for new anti-inflammatory therapies. We have shown previously that myristoylated alanine-rich C-kinase substrate (MARCKS), a well-known actin binding protein and protein kinase C (PKC) substrate, is a key regulator of Neutrophil functions. In the current study, we investigate the role of PKC-mediated MARCKS phosphorylation in Neutrophil Migration and adhesion in vitro . We report that treatment of human Neutrophils with the δ-PKC inhibitor rottlerin significantly attenuates f-Met-Leu-Phe (fMLF)-induced MARCKS phosphorylation (IC_50 = 5.709 μM), adhesion (IC_50 = 8.4 μM), and Migration (IC_50 = 6.7 μM), while α-, β-, and ζ-PKC inhibitors had no significant effect. We conclude that δ-PKC-mediated MARCKS phosphorylation is essential for human Neutrophil Migration and adhesion in vitro . These results implicate δ-PKC-mediated MARCKS phosphorylation as a key step in the inflammatory response of Neutrophils.
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Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Protein Regulation of Human Neutrophil Migration
American journal of respiratory cell and molecular biology, 2009Co-Authors: Rachael E. Eckert, Kenneth B Adler, Joungjoa Park, Laura E. Neuder, Samuel L. JonesAbstract:Neutrophil Migration into infected tissues is essential for host defense, but products of activated Neutrophils can be quite damaging to host cells. Neutrophil influx into the lung and airways and resultant inflammation characterizes diseases such as chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. To migrate, Neutrophils must reorganize the actin cytoskeleton to establish a leading edge pseudopod and a trailing edge uropod. The actin-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) has been shown to bind and cross-link actin in a variety of cell types and to co-localize with F-actin in the leading edge lamellipodium of migrating fibroblasts. The hypothesis that MARCKS has a role in the regulation of Neutrophil Migration was tested using a cell-permeant peptide derived from the MARCKS myristoylated aminoterminus (MANS peptide). Treatment of isolated human Neutrophils with MANS significantly inhibited both their Migration and β2 integrin-dependent adhesion i...