Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members

Este estudo se reporta às funções de células natural killer (NK), como adesão, lise e citotoxicidade e de subpopulações de células T em uma família com alta prevalência de pacientes com câncer e que apresentaram: glioblastoma, leucemia mielóide crônica, osteoblastoma, melanoma e carcinomas gástrico, pancreático e cólon retal. Quinze membros dessa família foram estudados, sendo 13 sadios, acompanhados por 5 anos e dois com câncer: glioblastoma e leucemia mielóide crônica. Duas pessoas sadias, no momento da avaliação, desenvolveram posteriormente osteoblastoma mandibular ou melanoma maligno. Como controle, foram avaliados 19 indivíduos saudáveis de faixa etária equivalente. A determinação de linfócitos T CD3+ e de suas subpopulações CD4+ e CD8+ foi realizada empregando-se anticorpos monoclonais e a atividade citotóxica de células NK, avaliada pelo teste de single-cell contra células alvo da linhagem eritroleucêmica K562. Os resultados mostraram que as percentagens de células T totais (CD3+), da subpopulação CD4+ e da relação CD4/CD8 foram significativamente menores nos indivíduos da família estudada em comparação aos valores observados no grupo controle. em todos os membros dessa família a percentagem de formação de conjugados entre células NK-células alvo foi inferior ao valor mínimo observado nos controles. Essa alteração poderia estar relacionada a defeito na expressão de moléculas de adesão, presentes na membrana de células NK, como provável causa das alterações funcionais dessas células. A herança dos mecanismos determinantes desta deficiência pode ser um fator de risco, com valor prognóstico para o desenvolvimento de cancer.

Subpopulations of mononuclear leukocytes associated with inhibition of Ehrlich ascites tumor growth by treatment with Bothrops jararaca venom

Snake venoms have been used as antineoplastic substances in several experimental models. We demonstrated in previous studies that Bothrops jararaca venom (BjV) induces inhibition of Ehrlich ascites tumor ( EAT) growth accompanied by an increase of mononuclear (MN) leukocytes in all groups inoculated with EAT and/or venom. The objective of the present study was to characterize the subpopulations of MN leukocytes involved in the inhibition of EAT growth by treatment with BjV. Swiss mice were inoculated with 1.0 x 10(3) EAT cells by the intraperitoneal route and treated with 0.4 mg/kg of BjV by the same route ( Group TV). Treatment was started 24 h after tumor cell inoculation and consisted of five intraperitoneal injections performed at 72 h intervals. After 2, 8 and 14 days, groups of animals were sacrificed and the number of B, TCD4 and TCD8 lymphocytes, macrophages and natural killer cells present in the peritoneal cavity was determined by flow cytometry. The control group consisted of animals inoculated with EAT and treated with 0.1 ml of saline under the same conditions as the experimental group ( Group T). Two additional control groups consisted of animals not inoculated with EAT and treated with saline or venom. Data were analyzed statistically by the Kruskal - Wallis nonparametric test for independent samples. on the 2nd and 8th day we observed a difference between groups T and TV ( group T > group TV) for all cell types, except natural killer cells, that only differed on the 2nd day. However, on the 14th day there was no difference in MN cells among groups. These data suggest that the inhibition of EAT is related to the toxic action of BjV on tumor cells and/or to the proteolytic effect of the venom on the mediators produced by the cells for growth modulation.

Imunidade inata da glândula mamária bovina: resposta à infecção

A imunidade na glândula mamária pode ser classificada, assim como em outros sistemas, em inata ou inespecífica e adaptativa ou específica. A imunidade inata é a defesa predominante durante os estágios iniciais da infecção. As respostas inespecíficas estão presentes no local da infecção ou são ativadas rapidamente por numerosos estímulos e não aumentam pela exposição repetida ao mesmo agente etiológico. O primeiro obstáculo enfrentado por um patógeno para adentrar o úbere é composto pela barreira formada pelo esfíncter do teto e pelo tampão de queratina formado pelo epitélio queratinizado. Uma vez que o microrganismo tenha atravessado o canal do teto e alcançado a cisterna mamária, passam a atuar diversos fatores solúveis e celulares. Dentre os fatores solúveis, estão presentes: lactoperoxidase, sistema complemento, citocinas, lactoferrina, lisozima e NAGase. As defesas celulares inespecíficas na glândula mamária são representadas pelos neutrófilos, pelos macrófagos e pelas células natural killer. Na medida em que esses mecanismos funcionam adequadamente, a maioria dos patógenos será rapidamente eliminada antes que o sistema imune específico seja ativado, sem resultar em alterações na quantidade ou qualidade do leite produzido. Uma melhor compreensão sobre os mecanismos de defesa da glândula mamária e suas alterações durante os períodos críticos da infecção é imprescindível para o desenvolvimento de métodos mais eficazes de profilaxia e controle da mastite, a principal doença dos ruminantes leiteiros. O presente estudo revisou os principais aspectos responsáveis pelo desenvolvimento da imunidade inata na glândula mamária bovina.

Propolis and the immune system: a review

Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. In recent years, in vitro and in vivo assays provided new information concerning its mechanisms of action, thus a review dealing with propolis and the immune system became imperative. This review compiles data from our laboratory as well as from other researchers, focusing on its chemical composition and botanical sources, the seasonal effect on its composition and biological properties, its immunomodulatory and antitumor properties, considering its effects on antibody production and on different cells of the immune system, involving the innate and adaptive immune response. In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity. Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production was demonstrated. Propolis inhibitory effects on lymphoproliferation may be associated to its anti-inflammatory property. In immunological assays, the best results were observed when propolis was administered over a short-term to animals. Propolis antitumor property and its anticarcinogenic and antimutagenic potential are discussed. Since humans have used propolis for different purposes and propolis-containing products have been marketed, the knowledge of its properties with scientific basis is not only of academic interest but also of those who use propolis as well. This review opens a new perspective on the investigation of propolis biological properties, mainly with respect to the immune system. (c) 2007 Elsevier B.V.. All rights reserved.

Hepatocyte lesions and cellular immune response in yellow fever infection

The study of the in-situ cellular immune response is very important for the understanding of different liver infections. In the present study, 53 liver samples obtained by viscerotomy from patients who died during the course of jungle yellow fever were analyzed. The diagnosis was confirmed by serology, viral isolation and virus-specific immunohistochemistry. The specimens were analyzed by immunohistochemistry using specific antibodies for apoptosis, CD45RO, CD4, CD8, CD20, S100, CD57 and CD68. Quantitative analysis of the labeling pattern showed a clear predominance of the different phenotypes in the portal tract and midzone region of the acini. There was a predominance of T CD4+ lymphocytes, accompanied by the presence of T CD8+ lymphocytes, natural killer cells (CD57), macrophages and antigen-presenting cells (S100). The disproportion between the intensity of inflammation and the degree of hepatic injury was probably due to the intense apoptotic component, which classically does not induce an inflammatory response. The present study demonstrates that, despite the disproportion between injury and inflammation, the cellular immune response plays an important role in the pathogenesis of the hepatocytic injury observed in yellow fever, probably as a result of cytolytic actions through mechanisms involving MHC II and the activation of Fas receptors and granzymes/perforins. (C) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Host-parasite relationships in paracoccidioidomycosis

A viewpoint of host-parasite relationships in paracoccidioidomycosis is presented. The characteristics of the fungus which are important to the host-parasite interaction are discussed. Aspects of inhibition of mycelium-to-yeast transformation by estrogens acting at receptors on the fungal wall and in the cytoplasm, and the role of polysaccharide components of the cell wall in virulence are reviewed. The natural mechanisms of host defense are also examined, including phagocytosis, complement system, natural-killer cells and genetic control of resistance and susceptibility. Finally, a discussion of granuloma morphogenesis and its relationship to the humoral and cellular anti-P. brasiliensis immune response is presented.

Suplementação alimentar de pacu (Piaractus mesopotamicus Holmberg, 1887) com β 1,3 glicano: atividade respiratória de leucócitos, lisozima e estresse por captura

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expressão imunohistoquímica de moléculas HLA não clássicas (HLA-G E HLA-E) e receptores CD4, CD28 em lesões de mucosa oral, associada a infecção pelo papilomavírus humano (HPV)

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Imunoterapia com a vacina heteróloga de DNA-HSP65+proteína-HSP65 de Mycobacterium leprae em tumores mamários de cadelas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Baixas Doses de 5-fluorouracil aumentam a atividade antitumoral de células dendríticas transfectadas com RNA de células de câncer colorretal

Pós-graduação em Patologia - FMB

Resposta imune diferenciada no fígado e no baço de cães com leishmaniose visceral

Pós-graduação em Medicina Veterinária - FCAV

KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Lack of Chemopreventive Activity of Agaricus blazei Mushroom on the Development of 1,2-Dimethylhydrazine-Induced Colonic Aberrant Crypt Foci in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HLA-G polymorphism and transitional cell carcinoma of the bladder in a Brazilian population

The morphologic appearance and clinical behavior of the human urinary bladder papillary transitional cell carcinoma (TCC) probably result from a complex interaction between carcinogenic insults and host resistance during the patient's life. While the main recognized risk factors are of environmental origin (e.g. smoking), relatively little information exists about the susceptibility to TCC development. The human leukocyte antigen G (HLA-G) molecule plays an important role in immune response regulation and has been implicated in the inhibition of the cytolytic function of natural killer and cytotoxic T cells. Several lines of evidence indicate that HLA-G polymorphisms influence the expression level and production of different HLA-G isoforms. The aim of this study was to explore a possible influence of the HLA-G polymorphism on the susceptibility to urinary bladder TCC development and progression in smokers and nonsmokers Brazilian subjects. The HLA-G locus was found to be associated with susceptibility to TCC development and progression. The G*0104 allelic group (specially the G*010404 allele) and the G*0103 allele were associated with a tobacco-dependent influence on TCC development. The G*0104 group was associated with progression to high-grade tumors, irrespective of smoking habit, while the G*0103 allele was associated to high-grade tumor only in smoking patients. Our results are an evidence that the HLA-G locus itself, or as part of an extended haplotype encompassing this chromosome region (particularly the HLA-A given the high linkage disequilibrium observed between them in this data series), may be associated with TCC susceptibility and tumor progression, suggesting a tobacco-dependent influence of these polymorphisms.

Effects of extracts from Brazilian sun-mushroom (Agaricus blazei) on the NK activity and lymphoproliferative responsiveness of Ehrlich tumor-bearing mice

Agaricus blazei Murrill, is an edible and medicinal mushroom which is popularly consumed due to its antitumoral properties. The immunomodulatory effects of methanol (METH), dichloromethane (DM) and n-hexane (HEX) extracts of this mushroom were evaluated in Ehrlich tumor-bearing mice. Subcutaneous inoculation of Ehrlich tumor cells inhibited the natural killer (NK) activity of spleen cells (specific lysis = 6.18 +/- 2.56%) compared with normal mice (17.59 +/- 7.77%). Treatment of tumor-bearing mice with the extracts for 10 days restored the natural killer activity against Yac-1 target cells and the best results were observed by treatment with the HEX extract (21.48 +/- 15.26%). Treatment of the animals with the HEX extract for 10 days was also able to stimulate the mitogen-induced lymphoproliferative activity of spleen cells. Thirty days after the treatment, all groups presented low proliferative activity. Specific antibody production was observed to be higher in the groups treated with the DM or METH extract 30 days after the treatment. Analysis of the 3 extracts by gas chromatography mass spectrum (GCMS) and magnetic nuclear resonance (MNR) showed that the HEX extract contains mainly sugar and fatty acids and that the METH extract also contains sugar and possibly amino acids. (C) 2004 Elsevier Ltd. All rights reserved.