A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2^{+} monocytes at a site of sterile injury

Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2^{hi}CX_{3}CR1^{low}) and nonclassical, patrolling, or alternative (CCR2^{low}CX_{3}CR1^{hi}) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2^{hi}CX_{3}CR1^{low} monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2^{hi}CX_{3}CR1^{low} to CX_{3}CR1^{hi}CCR2^{low} within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing

Avaliação do fosfato de rocha com baixo teor de flúor na alimentação de eqüinos em crescimento Evaluation of rock phosphate with low fluorine level in diets for growing horses

Utilizaram-se 18 potras com idade média de 11 meses e peso vivo médio de 250 kg, alimentadas com 3 dietas contendo fosfato bicálcico (FB); 50% de fosfato bicálcico mais 50% fosfato de rocha de Tapira (BT) e fosfato de rocha de Tapira (FT), incorporados ao concentrado (1,5% do peso vivo/animal/dia) e ao sal mineralizado (50 g/animal/dia). O nível médio de flúor nas dietas FB, BT e FT foi, respectivamente, de 53,0; 90,0 e 184,0 ppm. O consumo diferenciado de fluoreto nas diferentes dietas não acarretou efeitos sobre os parâmetros ganho de peso, perímetro torácico, perímetro do joelho e perímetro da canela. Os animais que receberam a dieta contendo exclusivamente fosfato de rocha apresentaram menor aumento de altura na cernelha (1,27cm) quando comparados àqueles que receberam dietas contendo fosfato bicálcico (1,55 e 1,30cm).<br>Eighteen fillies of <em>Brasileiro de Hipismo</em> breed with initial age between 9 and 12 months and 250kg of average weight were used in a complete block design, during a five-month trial to evaluate the use of three different inorganic phosphorus sources. The sources were dicalcium phosphate (FB), half and half dicalcium phosphate/Tapira rock phosphate mixture (BT) and Tapira rock phosphate (FT). They were added to a basal concentrate, given at the rate of 1.5% of average body weight and to a mineralized salt, of which 50 g/animal was offered daily. The mean fluoride level (concentrate plus salt) in diets FB, BT and FT was 53, 90 and 184 ppm respectively. The mean monthly withers height gain was 1.55 (FB), 1.30 (BT) and 1.27cm (FT) and there was a significant difference between FB and FT diets

Dual role of hydrogen sulfide in mechanical inflammatory hypernociception

Hydrogen Sulfide (H2S) is an endogenous gas involved in several biological functions, including modulation of nociception. However, the mechanisms involved in such modulation are not fully elucidated. The present Study demonstrated that the pretreatment of mice with PAG, a H2S synthesis inhibitor, reduced LPS-induced mechanical paw hypernociception. This inhibition of hypernociception was associated with the prevention of neutrophil recruitment to the plantar tissue. Conversely, PAG had no effect on LPS-induced production of the hypernociceptive cytokines, TNF-alpha, IL-1 beta and CXCL1/KC and on hypernociception induced by PGE(2), a directly acting hypernociceptive mediator. In contrast with the pro-nociceptive role of endogenous H2S. systemic administration of NaHS, a H2S donor, reduced LPS-induced mechanical hypernociception in mice. Moreover, this treatment inhibited mechanical hypernociception induced by PGE(2), suggesting a direct effect of H2S on nociceptive neurons. The antinociceptive mechanism of exogenous H2S depends on K-(ATP)(+) channels since the inhibition of PGE(2) hypernociception by NaHS was prevented by glibenclamide (K-(ATP)(+) channel blocker). Finally, NaHS did not alter the thermal nociceptive threshold in the hot-plate test, confirming that its effect is mainly peripheral. Taken together, these results suggest that H2S has a dual role in inflammatory hypernociception: 1. an endogenous pro-nociceptive effect due to up-regulation of neutrophil migration. and 2. an antinociceptive effect by direct blockade of nociceptor sensitization modulating K-(ATP)(+) channels. (c) 2008 Elsevier B.V. All rights reserved.FAPESPCNP

Anti-inflammatory activity and possible mechanism of extract from Mikania laevigata in carrageenan-induced peritonitis

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISObjectives The aim was to test the potential use of an extract of Mikania laevigata (popularly known in Brazil as guaco), made from leaves harvested in different months of the year, oil neutrophil migration after all inflammatory Stimulus and investigate the underlying molecular mechanisms. Methods We examined the effect of guaco on vascular permeability and leucocyte function in carrageenan-induced peritonitis in mice. Key findings Our results demonstrated that guaco extract administered subcutaneously (3 mg/kg) decreased the vascular permeability and also leucocyte rolling and adhesion to the inflamed tissues by a mechanism dependent on nitric oxide. Specifically, inhibitors of nitric oxide synthase remarkably abrogated the guaco extract-mediated suppression of neutrophil migration to the inflammatory site. In addition, guaco extract-mediated suppression of neutrophil migration appeared to be dependent on the production of the cytokines interleukin-1 beta and tumour necrosis factor-alpha. One of the major constituents of the guaco extract, coumarin, was able to inhibit the neutrophil migration towards the inflammatory focus. Conclusions In conclusion the anti-inflammatory effect induced by guaco extract may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.The aim was to test the potential use of an extract of Mikania laevigata (popularly known in Brazil as guaco), made from leaves harvested in different months of the year, oil neutrophil migration after all inflammatory Stimulus and investigate the underlying molecular mechanisms. We examined the effect of guaco on vascular permeability and leucocyte function in carrageenan-induced peritonitis in mice. Key findings Our results demonstrated that guaco extract administered subcutaneously (3 mg/kg) decreased the vascular permeability and also leucocyte rolling and adhesion to the inflamed tissues by a mechanism dependent on nitric oxide. Specifically, inhibitors of nitric oxide synthase remarkably abrogated the guaco extract-mediated suppression of neutrophil migration to the inflammatory site. In addition, guaco extract-mediated suppression of neutrophil migration appeared to be dependent on the production of the cytokines interleukin-1 beta and tumour necrosis factor-alpha. One of the major constituents of the guaco extract, coumarin, was able to inhibit the neutrophil migration towards the inflammatory focus. In conclusion the anti-inflammatory effect induced by guaco extract may be by inhibition of pro-inflammatory cytokine production at the inflammatory site61810971104CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPEMIG - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAISsem informaçãosem informaçã

Anti-inflammatory activity and possible mechanism of extract from Mikania laevigata in carrageenan-induced peritonitis

Objectives The aim was to test the potential use of an extract of Mikania laevigata (popularly known in Brazil as guaco), made from leaves harvested in different months of the year, oil neutrophil migration after all inflammatory Stimulus and investigate the underlying molecular mechanisms. Methods We examined the effect of guaco on vascular permeability and leucocyte function in carrageenan-induced peritonitis in mice. Key findings Our results demonstrated that guaco extract administered subcutaneously (3 mg/kg) decreased the vascular permeability and also leucocyte rolling and adhesion to the inflamed tissues by a mechanism dependent on nitric oxide. Specifically, inhibitors of nitric oxide synthase remarkably abrogated the guaco extract-mediated suppression of neutrophil migration to the inflammatory site. In addition, guaco extract-mediated suppression of neutrophil migration appeared to be dependent on the production of the cytokines interleukin-1 beta and tumour necrosis factor-alpha. One of the major constituents of the guaco extract, coumarin, was able to inhibit the neutrophil migration towards the inflammatory focus. Conclusions In conclusion the anti-inflammatory effect induced by guaco extract may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.PAPE-UNIUBE[2007/002]CAPESFundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)[34/07

Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta A(12,14)-prostaglandin J(2), reduces neutrophil migration via a nitric oxide pathway

Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) 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-PGJ(2)-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-PGJ(2) administration decreases leukocyte rolling and adhesion to the inflammated mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ(2)-mediated suppression of neutrophil migration to the inflammatory site. Moreover, inducible NOS(-/-) mice were not susceptible to 15d-PGJ(2)-mediated suppression of neutrophil migration to the inflammatory sites when compared with their wild type. In addition, 15d-PGJ(2)-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-I expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ(2), whereas 15d-PGJ(2) inhibited F-actin rearrangement process in neutrophils. Taken together these findings demonstrated that 15d-PGJ(2) suppresses inflammation-initiated neutrophil migration in a mechanism dependent on NO production in mesenteric tissues

Peroxisome proliferator-activated receptor-γ ligand, 15-deoxy-Δ12,14-prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway

Ligands for peroxisome proliferator-activated receptor γ (PPAR-γ), such as 15-deoxy-Δ12,14-prostaglandin J 2 (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-PGJ 2-mediated activation of PPAR-γ 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-PGJ 2 administration decreases leukocyte rolling and adhesion to the inflammated mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ 2-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-PGJ 2-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, upregulation of carrageenan-triggered ICAM-1 expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ2, whereas 15d-PGJ 2 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. Copyright © 2007 by The American Association of Immunologists, Inc