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Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(3): 766-70, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-20561447


After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.

Modelos Animais de Doenças , Sepse , Animais , Apoptose , Ceco/lesões , Complemento C5a/metabolismo , Interferon gama/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/metabolismo , Sepse/patologia , Baço/patologia , Timo/patologia , Fator de Necrose Tumoral alfa/metabolismo
Acta Pharmacol Sin ; 28(10): 1611-20, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17883948


AIM: To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo. METHODS: Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models. RESULTS: The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cell-mediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo. CONCLUSION: The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.

Fragmentos de Imunoglobulinas/imunologia , Interleucina-2/imunologia , Neoplasias Ovarianas/prevenção & controle , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Animais , Citotoxicidade Celular Dependente de Anticorpos , Linhagem Celular Tumoral , Feminino , Humanos , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/metabolismo , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Região Variável de Imunoglobulina/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
Cell Mol Immunol ; 2(6): 461-5, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16426497


CD3-specific monoclonal antibody was the first one used for clinical practice in field of transplantation. Recently, renewed interests have elicited in its capacity to prevent autoimmune diabetes by inducing immune tolerance. In this study, we tested whether this antibody can also be used to treat another kind of autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms. MG is caused by an autoimmune damage mediated by antibody- and complement-mediated destruction of AChR at the neuromuscular junction. We found that administration of CD3-specific antibody (Fab)2 to an animal model with experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of AChR/CFA immunization) could not significantly improve the clinical signs and clinical score. When the possible mechanisms were tested, we found that CD3 antibody treatment slightly down-regulated the T-cell response to AChR, modestly up-regulating the muscle strength. And no significant difference in the titers of IgG2b was found between CD3 antibody treated and control groups. These data indicated that CD3-specific antibody was not suitable for treating MG, an antibody- and complement- mediated autoimmune disease, after this disease has been established. The role of CD3-specific antibody in treating this kind of disease remains to be determined.

Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Complexo CD3/imunologia , Miastenia Gravis Autoimune Experimental/tratamento farmacológico , Miastenia Gravis Autoimune Experimental/imunologia , Animais , Proliferação de Células/efeitos dos fármacos , Eletromiografia , Feminino , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Camundongos , Miastenia Gravis Autoimune Experimental/diagnóstico , Miastenia Gravis Autoimune Experimental/prevenção & controle , Baço/citologia , Baço/efeitos dos fármacos