HIRO GOTO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Medicina Preventiva, Faculdade de Medicina - Docente
LIM/38 - Laboratório de Epidemiologia e Imunobiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/38 - Laboratório de Epidemiologia e Imunobiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion(2011) TORRINHAS, R. S.; JACINTHO, T.; GOTO, H.; GIDLUND, M.; SALES, M. M.; OLIVEIRA, P. A.; WAITZBERG, D. L.Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (M phi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium-chain trygliceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-g addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on MO surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 05%: 100) FO decreased the expression of HLA-DR when added alone in simultaneously-activated M., for 0.1%: 70 (59 +/- 73); for 0.25%: 51 (48 +/- 56); and for 05%: 52.5 (50 +/- 58)1 or in association with MCTSO [in simultaneously-activated MO, for 0.1%: 50.5 (47 +/- 61); for 25%: 49 (45 +/- 52); and for 0.5%: 51 (44 54) and in previously-activated Mf, for 1.0%: 63 (44 +/- 88); for 0.25%: 70 (41 +/- 88); and for 0.5%: 59.5 (39 +/- 79)1 in culture medium (Friedman p < 0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated M phi [for 0.1%: 87.5(75 +/- 93); for 0.25%: 111 (98 +/- 118); and for 0.5%: 101.5 (84 +/- 113)]. Results show that parenteral FO modulates the expression of HLA-DR on human MO surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.
article 8 Citação(ões) na Scopus Leptospirosis Infection in Sheep and Characterization of the Renal Inflammatory Response.(2011) CARVALHO, Sonia Maria de; GONCALVES, Larissa Maria Feitosa; MACEDO, Nicodemos Alves de; GOTO, Hiro; SILVA, Silvana Maria Medeiros de Sousa; MINEIRO, Ana Lys Bezerra Barradas; KANASHIRO, Edite Hatsumi Yamashiro; COSTA, Francisco Assis LimaCarvalho S.M., Gon alves L.M.F., Macedo N.A., Goto H., Silva S.M.M.S., Mineiro A.L.B.B., Kanashiro E.H.Y. & Costa F.A.L. 2011. [Leptospirosis Infection in Sheep and Characterization of the Renal Inflammatory Response.] Infeccao por leptospiras em ovinos e caracterizacao da resposta inflamatoria renal. Pesquisa Veterinaria Brasileira 31(8):637-642. Departamento de Clinica e Cirurgia Veterinaria, Centro de Ciencias Agrarias, Universidade Federal do Piaui, Campus Socopo, Teresina, PI 64046-550, Brazil. E-mail: fassisle@gmail.com Lepitospirosis is a serious worldwide distribution disease which affects man and other animals. The infection is generally asymptomatic in animals. In cases whose symptoms are present, symptoms are similar to other infections. In the present study serum samples from 119 sheep and their kidneys were collected during their slaughter in outdoor markets in the city of Teresina, Piaui, Brazil. The Microscopic Agglutination Test (MAT) obtained 34 positive serological samples for one or more Leptospira spp. serovar with occurrence rate of 28.6% of leptospiral antibodies. There were 23 cases of infection for a single serovar, and 11 cases with coagglutination for two or more serovars. Autumnalis had the highest occurrence (29.4%) among the pathogenic serovars. The histopathological analysis of 36 kidney fragments revealed tubulo-interstitial alterations in 33 (91.7%) positive animals. Tubular lesions were observed in 20 (55.5%) positive animals. The Warthin Starry staning revealed the presence of Leptospira in 8 (22.20%) of the 36 positive samples. The immunoperoxidase staining revealed the presence of Leptospira in 12 (60%) of 20 positive samples. The inflammatory infiltrate in the positive animals was significantly more evident in the cortical-medullar and cortical regions than in the medullar region (p=0.000), however, there was no difference between positive and negative animals. The presence of hyaline casts in the proximal tubules was significantly higher in positive animals compared to the negative ones (p=0.0001). Discrete lesion was observed in glomeruli. In conclusion, the results from this study showed that sheep which are positive for Leptospira present tubulo-intersticial renal lesions with the presence of Leptospira in the tubules, conferring to these animals the condition of asymptomatic carriers.- Protein Disulfide Isomerase and Host-Pathogen Interaction(2011) STOLF, Beatriz S.; IOANNIS, Smyrnias; LOPES, Lucia R.; VENDRAMIN, Alcione; GOTO, Hiro; LAURINDO, Francisco R. M.; SHAH, Ajay M.; SANTOS, Celio X. C.Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i. e., intra-and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections.
- Dynamics of immunosuppression in hamsters with experimental visceral leishmaniasis(2011) FAZZANI, C.; GUEDES, P. A.; SENA, A.; SOUZA, E. B.; GOTO, H.; LINDOSO, J. A. L.Immunosuppression has been reported to occur during active visceral leishmaniasis and some factors such as the cytokine profile may be involved in this process. In the mouse model of cutaneous leishmaniasis using Leishmania (Leishmania) major, the Th1 response is related to protection while the Th2 response is related to disease progression. However, in hamsters, which are considered to be an excellent model for the study of visceral leishmaniasis, this dichotomy is not observed. Using outbred 45- to 60-day-old (140 to 150 g) male hamsters infected intraperitoneally with 2 x 10(7) L. (L.) chagasi amastigotes, we evaluated the immune response of spleen cells and the production of cytokines. We used 3 to 7 hamsters per group evaluated. We detected a preserved response to concanavalin A measured by index of proliferation during all periods of infection studied, while a proliferative response to Leishmania antigen was detected only at 48 and 72 h post-infection. Messenger RNA from cytokines type 1 (IL-2, TNF-alpha, IFN-gamma) and type 2 (IL-4, IL-10 and TGF-beta) detected by reverse transcriptase polymerase chain reaction and produced by spleen cells showed no qualitative difference between control non-infected hamsters and infected hamsters during any period of infection evaluated. Cytokines were measured by the DNA band intensity on agarose gel using the Image Lab 1D L340 software with no differences observed. In conclusion, the present results showed an antigen-dependent immunosuppression in hamsters with active visceral leishmaniasis that was not related to the cytokine profile.