No description available.

Les maladies thrombotiques sont la cause majeure de décès dans les pays industrialisés. Les cellules souches dérivées de la moelle osseuse ont été impliqués dans la réparation vasculaire et contribuent à restaurer l'intégrité de l'endothélium. Les cellules progéniteurs CD34 positives ont été rapportées pour jouer un rôle important suite à une blessure de la paroi vasculaire en se liant aux plaquettes ou à la fibrine, modulant la formation du thrombus et participant à la ré-endothélialisation de la paroi vasculaire lésée. Parmi les cellules progéniteurs CD34 positives, les cellules endothéliales formant colonie (ECFC) ont été caractérisés comme présentant des propriétés endothéliale. La première partie de ce travail met en évidence un nouveau partenariat entre les neutrophiles et les ECFC. Par l'utilisation de la microscopie intravitale chez les souris, nous montrons que les neutrophiles recrutent les ECFC au site de lésion vasculaire induite par rayon laser. Ce recrutement est dépendant du PSGL-1 mais indépendant de l'expression de la P-sélectine. L'interaction avec les neutrophiles accroît le potentiel pro-angiogénique des ECFC in vitro. L'identification de ce nouveau partenariat entre les neutrophiles et les ECFC dans la formation de thrombus possède des implications potentiellement critiques dans le contrôle de l'angiogenèse.
La seconde partie de ce travail décrit une nouvelle méthode pour imager en temps réel le devenir des ECFCs in vivo. Nos résultats montrent que les ECFC s'accumule au site de lésion vasculaire.
En conclusion, ce travail démontre que les ECFC peuvent participer favoriser et réguler l'angiogenèse en interagissant avec les neutrophiles. / Thrombotic diseases are major cause of death in industrialized countries. Bone marrow derived progenitor cells have been implicated in vascular repair and contribute to restore the integrity of endothelium, thus constituting important partners for vascular wall restoration. CD34 positive progenitors cells were reported to play an important role following an injury of the vessel wall by binding to platelets or fibrin, modulating thrombus formation and participating in the re-endothelization of the injured vessel wall. Among CD34 positive progenitors cells, Endothelial Colony forming Cells (ECFCs) have been characterized as a unique subset displaying endothelial properties. The first part of this work described a new partnership between neutrophils and ECFCs. Using high- speed digital fluorescent intravital microscopy in living mice we show that neutrophils recruit ECFCs at the site of a laser-induced vessel injury via PSGL-1 axis independently of P-selectin. This interaction enhances the pro-angiogenic potential of ECFCs in vitro. The identification a new central partnership between neutrophils and ECFC in thrombus formation has critical potential implications to control angiogenesis.
The second part of this work, described a new method to image in real-time the homing and survival ECFCs in vivo. Our results show that ECFCs transducted with a gene coding for luciferase accumulates at site of vascular traumatism.
In conclusion, this work indicates that ECFCs may participate in the promotion and regulation of angiogenesis by interacting with neutrophils at a site of vascular traumatism.

Além dos receptores no sistema nervoso central (SNC), acoplados a receptores GABAA (CBR - central benzodiazepine receptor), outros sítios periféricos de ligação para os benzodiazepínicos (BDZ) foram descritos e denominados de \"periféricos\" (PBR peripheral benzodiazepine receptor) ou TSPO - Translocator protein. Sua função como modulador do sistema imune tem sido proposta, com a participação, pelo menos em parte, de glicocorticóides endógenos (GE). No entanto, os mecanismos da modulação dos TSPO sobre o processo inflamatório e a relação destes receptores com os GE ainda não estão totalmente estabelecidos. Desta forma, este trabalho visou investigar os efeitos de dois ligantes sintéticos de TSPO, um benzodiazepínico, Ro5-4864, e uma isoquinolona carboxamida, PK 11195, e suas relações com os GE, sobre os eventos da migração leucocitária. Para tanto, ratos Wistar machos foram tratados in vivo com RU 38486 (antagonista de receptor de GE) ou com veículo e, adicionalmente, os ligantes de TSPO, Ro5-4864 e/ou PK 11195, foram aplicados topicamente sobre a microcirculação do mesentério dos animais para avaliação do comportamento rolling e aderência de leucócitos, por microscopia intravital, em condições basais ou após estimulação pelo peptídeo formil-metionil-leucilfenilalanina (fMLP). Leucócitos periféricos foram coletados e tratados in vitro com os ligantes de TSPO para avaliação da expressão de moléculas de adesão, quimiotaxia e influxo de cálcio em condições basais ou após estimulação pelo fMLP. Ainda, culturas primárias de células endoteliais da microcirculação de ratos foram tratadas in vitro com os ligantes de TSPO para avaliação da expressão de moléculas de adesão em condições basais ou após estimulação pelo lipopolisacarídeo de E.coli (LPS). Os resultados obtidos mostraram que: 1) o ligante de TSPO, Ro5-4864, alterou a ação do fMLP, uma vez que inibiu a diminuição do rolling, o aumento de células aderentes, a clivagem de L-selectina, o aumento de expressão de PECAM-1 (platelet endothelial cell adhesion molecule), a quimiotaxia e o influxo de cálcio em neutrófilos; não afetou a expressão de PECAM-1 e ICAM-1 (intracellular cell adhesion molecule) induzida pelo LPS em células endoteliais; 2) o PK 11195 aumentou o influxo de cálcio e a quimiotaxia de neutrófilos induzido pelo fMLP; 3) a co-administração dos ligantes de TSPO, Ro5-4864 e PK 11195, reverteu os efeitos do Ro5-4864 sobre a expressão de L-selectina e PECAM-1, o influxo de cálcio e a quimiotaxia de neutrófilos. A possível inter-relação dos TSPO e GE foi verificada uma vez que o Ro5-4864 inibiu o aumento do número de leucócitos rolling e aderidos à parede vascular in vivo causado pelo tratamento com RU 38486; inibiu o aumento da expressão de L-selectina em neutrófilos e de β2-integrina presente em linfócitos e de PECAM-1 em neutrófilos. Ainda, foi verificado que neutrófilos possuem expressões de TSPO maiores que linfócitos e células endoteliais e que esta expressão é aumentada em neutrófilos pela ação do fMLP. Em conjunto, os resultados obtidos neste trabalho sugerem que os ligantes de TSPO modulam diferentemente as funções de adesão e mobilidade de leucócitos e de adesão da célula endotelial e que uma relação alostérica de agonismo/antagonismo entre estes pode ser sugerida. Adicionalmente, os resultados mostram uma possível relação entre os TSPO e os receptores de citoplasmáticos de GE no controle da interação leucócito-endotélio. / Besides central benzodiazepine receptor (CBR) found on central nervous system (CNS) coupled to GABAA, another binding site for benzodiazepines was described and named peripheral benzodiazepine receptor (PBR) or Translocator protein (TSPO). The mainly function described to this TSPO is steroidogenesis. Additionally, its function as an immune modulator has been proposed with the involvement, at least in part, of endogenous glucocorticoids (EG). However, mechanisms of TSPO modulation on inflammatory process and the relation between the receptor and EG has not been totally established. This study aimed investigates effects of two synthetic TSPO ligands, a benzodiazepine, Ro5-4864, and an isoquinoline carboxamide, PK 11195, and their relation with EG on leukocyte migration. For this purpose, male Wistar rats were in vivo treated with RU 38486 (EG antagonist receptor) or vehicle and, in addition, TSPO ligands, Ro5-4864 and/or PK 11195, were topically applied on animal mesentery microcirculation to evaluate leukocyte rolling and adhesion, by intravital microscopy, under basal conditions or after stimulation by N-formyl-methionine-leucine-phenylalanine (fMLP). In addition, peripheral leukocytes were collected and in vitro treated with TSPO ligands to evaluate adhesion molecules expression, chemotaxis and calcium influx. Endothelial cells obtained from cremaster muscle were in vitro treated with TSPO ligands to evaluate adhesion molecules expression under basal conditions or after stimulation by lipopolysaccharide from E.coli (LPS). Our results showed that: 1) TSPO ligand, Ro5-4864, altered the fMLP action since TSPO ligand inhibited the decrease of rolling, the increase of adherent cells, L-selectin cleavage, the increase of PECAM-1 expression, neutrophil chemotaxis and calcium influx; did not affect expression of PECAM-1 and ICAM-1 induced by LPS on endothelial cells; 2) PK 11195 increased fMLP-induced neutrophil calcium influx and chemotaxis; 3) co-administration of TSPO ligands, Ro5-4864 and PK 11195, reverted Ro5-4864 effects on L-selectin and PECAM-1 expression, neutrophil and calcium influx, as well as PECAM-1 and ICAM-1 expression on endothelial cells; 3) a possible inter-relation between TSPO and EG was observed since Ro5-4864 inhibited the increase of in vivo leukocyte rolling and adhesion induced by RU 38486 in vivo treatment; it inhibited the increase of neutrophil L-selectin, lymphocyte β2-integrin and leukocyte PECAM-1 expressions; 4) It was showed that neutrophil have more TSPO than lymphocytes and endothelial cells, and this expression is increased by fMLP stimulation. Taken together, our results suggest that TSPO ligands differently modulate leukocyte adhesion and motility functions and endothelial cells adhesion, and further, they suggest an allosteric agonist/antagonist relation. Additionally, they showed a relation between TSPO and EG cytoplasmic receptor on the control of leukocyte-endothelial interaction.

Além dos receptores no sistema nervoso central (SNC), acoplados a receptores GABAA (CBR - central benzodiazepine receptor), outros sítios periféricos de ligação para os benzodiazepínicos (BDZ) foram descritos e denominados de \"periféricos\" (PBR peripheral benzodiazepine receptor) ou TSPO - Translocator protein. Sua função como modulador do sistema imune tem sido proposta, com a participação, pelo menos em parte, de glicocorticóides endógenos (GE). No entanto, os mecanismos da modulação dos TSPO sobre o processo inflamatório e a relação destes receptores com os GE ainda não estão totalmente estabelecidos. Desta forma, este trabalho visou investigar os efeitos de dois ligantes sintéticos de TSPO, um benzodiazepínico, Ro5-4864, e uma isoquinolona carboxamida, PK 11195, e suas relações com os GE, sobre os eventos da migração leucocitária. Para tanto, ratos Wistar machos foram tratados in vivo com RU 38486 (antagonista de receptor de GE) ou com veículo e, adicionalmente, os ligantes de TSPO, Ro5-4864 e/ou PK 11195, foram aplicados topicamente sobre a microcirculação do mesentério dos animais para avaliação do comportamento rolling e aderência de leucócitos, por microscopia intravital, em condições basais ou após estimulação pelo peptídeo formil-metionil-leucilfenilalanina (fMLP). Leucócitos periféricos foram coletados e tratados in vitro com os ligantes de TSPO para avaliação da expressão de moléculas de adesão, quimiotaxia e influxo de cálcio em condições basais ou após estimulação pelo fMLP. Ainda, culturas primárias de células endoteliais da microcirculação de ratos foram tratadas in vitro com os ligantes de TSPO para avaliação da expressão de moléculas de adesão em condições basais ou após estimulação pelo lipopolisacarídeo de E.coli (LPS). Os resultados obtidos mostraram que: 1) o ligante de TSPO, Ro5-4864, alterou a ação do fMLP, uma vez que inibiu a diminuição do rolling, o aumento de células aderentes, a clivagem de L-selectina, o aumento de expressão de PECAM-1 (platelet endothelial cell adhesion molecule), a quimiotaxia e o influxo de cálcio em neutrófilos; não afetou a expressão de PECAM-1 e ICAM-1 (intracellular cell adhesion molecule) induzida pelo LPS em células endoteliais; 2) o PK 11195 aumentou o influxo de cálcio e a quimiotaxia de neutrófilos induzido pelo fMLP; 3) a co-administração dos ligantes de TSPO, Ro5-4864 e PK 11195, reverteu os efeitos do Ro5-4864 sobre a expressão de L-selectina e PECAM-1, o influxo de cálcio e a quimiotaxia de neutrófilos. A possível inter-relação dos TSPO e GE foi verificada uma vez que o Ro5-4864 inibiu o aumento do número de leucócitos rolling e aderidos à parede vascular in vivo causado pelo tratamento com RU 38486; inibiu o aumento da expressão de L-selectina em neutrófilos e de β2-integrina presente em linfócitos e de PECAM-1 em neutrófilos. Ainda, foi verificado que neutrófilos possuem expressões de TSPO maiores que linfócitos e células endoteliais e que esta expressão é aumentada em neutrófilos pela ação do fMLP. Em conjunto, os resultados obtidos neste trabalho sugerem que os ligantes de TSPO modulam diferentemente as funções de adesão e mobilidade de leucócitos e de adesão da célula endotelial e que uma relação alostérica de agonismo/antagonismo entre estes pode ser sugerida. Adicionalmente, os resultados mostram uma possível relação entre os TSPO e os receptores de citoplasmáticos de GE no controle da interação leucócito-endotélio. / Besides central benzodiazepine receptor (CBR) found on central nervous system (CNS) coupled to GABAA, another binding site for benzodiazepines was described and named peripheral benzodiazepine receptor (PBR) or Translocator protein (TSPO). The mainly function described to this TSPO is steroidogenesis. Additionally, its function as an immune modulator has been proposed with the involvement, at least in part, of endogenous glucocorticoids (EG). However, mechanisms of TSPO modulation on inflammatory process and the relation between the receptor and EG has not been totally established. This study aimed investigates effects of two synthetic TSPO ligands, a benzodiazepine, Ro5-4864, and an isoquinoline carboxamide, PK 11195, and their relation with EG on leukocyte migration. For this purpose, male Wistar rats were in vivo treated with RU 38486 (EG antagonist receptor) or vehicle and, in addition, TSPO ligands, Ro5-4864 and/or PK 11195, were topically applied on animal mesentery microcirculation to evaluate leukocyte rolling and adhesion, by intravital microscopy, under basal conditions or after stimulation by N-formyl-methionine-leucine-phenylalanine (fMLP). In addition, peripheral leukocytes were collected and in vitro treated with TSPO ligands to evaluate adhesion molecules expression, chemotaxis and calcium influx. Endothelial cells obtained from cremaster muscle were in vitro treated with TSPO ligands to evaluate adhesion molecules expression under basal conditions or after stimulation by lipopolysaccharide from E.coli (LPS). Our results showed that: 1) TSPO ligand, Ro5-4864, altered the fMLP action since TSPO ligand inhibited the decrease of rolling, the increase of adherent cells, L-selectin cleavage, the increase of PECAM-1 expression, neutrophil chemotaxis and calcium influx; did not affect expression of PECAM-1 and ICAM-1 induced by LPS on endothelial cells; 2) PK 11195 increased fMLP-induced neutrophil calcium influx and chemotaxis; 3) co-administration of TSPO ligands, Ro5-4864 and PK 11195, reverted Ro5-4864 effects on L-selectin and PECAM-1 expression, neutrophil and calcium influx, as well as PECAM-1 and ICAM-1 expression on endothelial cells; 3) a possible inter-relation between TSPO and EG was observed since Ro5-4864 inhibited the increase of in vivo leukocyte rolling and adhesion induced by RU 38486 in vivo treatment; it inhibited the increase of neutrophil L-selectin, lymphocyte β2-integrin and leukocyte PECAM-1 expressions; 4) It was showed that neutrophil have more TSPO than lymphocytes and endothelial cells, and this expression is increased by fMLP stimulation. Taken together, our results suggest that TSPO ligands differently modulate leukocyte adhesion and motility functions and endothelial cells adhesion, and further, they suggest an allosteric agonist/antagonist relation. Additionally, they showed a relation between TSPO and EG cytoplasmic receptor on the control of leukocyte-endothelial interaction.

Submitted by Luciana Sebin (lusebin@ufscar.br) on 2016-10-10T19:45:24Z No. of bitstreams: 1 DissKES.pdf: 1491828 bytes, checksum: c6a58b88ab03eb7890e0b182f08a3ab3 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-13T20:15:20Z (GMT) No. of bitstreams: 1 DissKES.pdf: 1491828 bytes, checksum: c6a58b88ab03eb7890e0b182f08a3ab3 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-13T20:15:29Z (GMT) No. of bitstreams: 1 DissKES.pdf: 1491828 bytes, checksum: c6a58b88ab03eb7890e0b182f08a3ab3 (MD5) / Made available in DSpace on 2016-10-13T20:15:42Z (GMT). No. of bitstreams: 1 DissKES.pdf: 1491828 bytes, checksum: c6a58b88ab03eb7890e0b182f08a3ab3 (MD5) Previous issue date: 2016-02-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Counting the number of leukocytes present in the blood vessels is an important task to understand inflammation mechanisms and to assess the effects of drugs that are being developed for the treatment of inflammatory diseases. In general, leukocyte counting is done by an observer (laboratory technician or specialist) using a sequence of intravital microscopy images obtained from blood vessel of an animal testing. However, this procedure is time-consuming, prone to errors, due to visual fatigue of the observer, and biased, due to inter and intra-observer variability. Thus, the objective of this work was the development of computational technique for the automatic detection of leukocytes in intravital video microscopy images. For this, the detection of leukocytes was performed in two main stages. In stage 1, the phase congruency measure, which is invariant to changes of contrast and lighting images, was used to calculate a blobness measure used to detect circular structures in intravital microscopy images. In stage 2, the circular structures detected in stage 1 were analyzed locally to identify only those corresponding to true leukocytes. The results were evaluated using the precision, recall and F1-measure metrics and the area under the precision-recall curves. Furthermore, the proposed technique was compared with the template matching technique. / Contar o número de leucócitos presentes em vasos sanguíneos é uma tarefa fundamental para entender mecanismos de inflamações e avaliar efeitos de drogas que estão sendo desenvolvidas para o tratamento de doenças inflamatórias. Em geral, a contagem de leucócitos é feita por um observador (técnico laboratorial ou especialista) usando uma sequência de imagens de microscopia intravital, obtidas do vaso sanguíneo de um animal de teste. Entretanto, a tarefa de contagem é demorada, propensa à erros, devido à fadiga visual do observador, e viesada, devido à variabilidade inter e intra-observador. Sendo assim, o objetivo deste trabalho foi o desenvolvimento de uma técnica computacional para a detecção automática de leucócitos em imagens de vídeo de microscopia intravital. Para isso, a detecção dos leucócitos foi realizada em dois principais estágios. No estágio 1, a medida de congruência de fase, que é invariante a mudanças de contraste e iluminação em imagens, foi utilizada para o cálculo de uma medida de blobness usada na detecção de estruturas circulares nas imagens de microscopia intravital. No estágio 2, as estruturas circulares detectadas no estágio 1 foram analisadas localmente a fim de identificar apenas aquelas correspondentes aos leucócitos verdadeiros. Os resultados foram avaliados utilizando as métricas de precisão, revocação e medida-F1 e a área sob as curvas precisão-revocação. Além disso, a técnica proposta foi comparada com a técnica casamento de padrões.

Malaria affects 200 million people annually, resulting in 584,000 - 1,238,000 deaths. The majority of these deaths occur in children, less than 5 years of age, in sub-Saharan Africa and are due to cerebral malaria (CM), a neuropathology induced primarily by the species Plasmodium (P.) falciparum. The pathogenesis of CM remains poorly understood and the mechanisms involved in acquired protection against the syndrome in malaria-endemic regions are undefined. Utilising the well characterised P. berghei ANKA experimental infection model of cerebral malaria (ECM), results presented in this thesis show that the development of ECM is associated with the accumulation and arrest of pathogenic CD8+ T cells within the perivascular spaces of the brain. Accumulation of activated CD8+ T cells, without arrest, was observed in the perivascular spaces of the brains of mice infected with the non-ECM causing P. berghei NK65 strain. These data show that the behaviour of intracerebral CD8+ T cells specifies their pathogenic function during malaria infection. The development of ECM was associated with extensive disruption to the BBB, which developed in the absence of extensive CD8+ T cell-dependent endothelial cell apoptosis. We modified the ECM model, establishing an infection-drug cure strategy, to investigate the immunological basis of parasite exposure-induced resistance to ECM development. Three rounds of infection-drug cure promoted resistance to ECM, which was associated with reduced intracerebral expression of genes involved in defence response, regulation of apoptosis, chemotaxis, CTL activity, antigen processing and presentation and cell adhesion, compared with ECM susceptible mice. Additionally, CD8+ T cell activation was suppressed in exposure-induced resistant mice and was associated with the antibody dependent expansion of a splenic plasmacytoid DC population, with a regulatory phenotype. The infection-induced protection against ECM was critically dependent upon secreted antibody production. A long standing problem in studying the immune response to malaria infection has been the inability to track parasite-specific CD4+ T cell responses. To address this, we generated and validated new transgenic P. berghei parasites expressing the model antigen, ovalbumin (OVA), either in the parasite cytoplasm or on the parasitophorous vacuole membrane (PVM). We found that cellular location and expression level of the antigen influence the induction and magnitude of parasite-specific T-cell responses. These parasites thus provide knowledge on the factors that influence the recognition of parasite antigens by the immune system and represent useful tools to study the development and function of antigen-specific T-cell responses during malaria infection. The results in this thesis improve our understanding of the events that lead to the development of CM, and the host immune responses that develop following parasite exposure to protect against it. The results should contribute towards the rational development of adjunctive therapies and effective vaccines for human CM.

Submitted by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-06-14T14:37:43Z No. of bitstreams: 1 Publico-39222.pdf: 1977138 bytes, checksum: fc8aa8b1fdd51076eef8be3cb204c292 (MD5) / Approved for entry into archive by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-06-14T14:39:39Z (GMT) No. of bitstreams: 1 Publico-39222.pdf: 1977138 bytes, checksum: fc8aa8b1fdd51076eef8be3cb204c292 (MD5) / Made available in DSpace on 2016-06-14T14:39:39Z (GMT). No. of bitstreams: 1 Publico-39222.pdf: 1977138 bytes, checksum: fc8aa8b1fdd51076eef8be3cb204c292 (MD5) Previous issue date: 2007 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: Muitos pacientes ainda morrem devido a infecções. Crescentes relatos da literatura atual têm atribuído ao intestino o papel de agravamento de doenças graves, e/ou a sua participação na gênese da sepse por mecanismo de translocação bacteriana (TB). Objetivo: Avaliar de forma cinética a TB e suas repercussões microcirculatórias e imunológicas. Método: Ratos Wistar-EPM (n=162) foram aleatoriamente distribuídos em grupo Sham (n=72) e grupo TB (n=90), e avaliados nos períodos de 2h, 6h, 24h, 72h, 7 e 14 dias, em relação a índice de translocação bacteriana; microscopia intravital; perfusão tecidual; e componentes celulares e humorais da linfa mesentérica por linfograma, citometria de fluxo e CBA-Flex. Resultado: A TB ocorreu somente no grupo TB e foi expressiva nas primeiras 24 horas tornando-se negativa somente com 7 dias. A conseqüência de um episódio de TB repercutiu na celularidade e citocinas pró e antiinflamatórias da linfa mesentérica associado a lesões da microcirculação e hipoperfusão tecidual de forma local e sistêmica. A citometria de fluxo mostrou que a linfa mesentérica eferente pós TB difere significativamente do grupo Sham quanto a número e subpopulação de linfócitos. Conclusão: Um episódio agudo de TB determinou uma recuperação máxima bacteriana com 6 horas e sua completa depuração entre 3 e 7 dias, além de provocar alterações da microcirculação intestinal e sistêmica associadas à ativação do GALT, principalmente no período de permanência das bactérias translocadas no hospedeiro, sendo a via linfática mesenterial uma importante rota na intercomunicação imunológica entre o ambiente intestinal e sistêmico. / Introduction: Many patients still die from infection. Currently, growing evidences have pointed out the role of the gut in the worsening of the critical illness, and/or its participation in the genesis of the bacterial translocation. Objective: Evaluate the bacterial translocation (BT) kinetics and its repercussion on microcirculation and immune response. Method: Wistar-EPM rats (n=162) were randomly distributed in Sham group (n=72) and BT group (n=90), and were monitored at 2h, 6h, 24h, 72h, 7 and 14 days periods in relation to bacterial translocation index, intravital microscopy, tissue perfusion index, and cellular and humoral components of the mesenteric lymph by lymphogram, flow cytometry and CBA-Flex. Results: Bacterial recovery was positive only in BT-group and it was expressive in the first 24 hours, becoming negative only after seven days. The consequences of one episode of BT could be seen in the cellularity and proinflammatory and antiinflammatory citokines of the efferent mesenteric lymph associated to local and systemic microcirculation and tissue hypoperfusion. The flow cytometry showed that efferent mesenteric lymph after BT was significantly different as compared to Sham group in relation to lymphocites number and their subtype. Conclusion: An acute episode of BT determined maximal bacterial recovery at 6h and its complete clearance occurred between 3 and 7 days, in addition to the gut and systemic microcirculation injuries due to the GALT activation, specially at the presence of translocated bacteria in the host, demonstrating the importance of the lymphatic route in the immune crosstalk between the gut and systemic enviroment. / FAPESP: 05/53826-7

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20242号 / 医博第4201号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 岩井 一宏, 教授 楠見 明弘 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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No description available.