RESUMO
To clarify the mechanism of action of an intravenous immunoglobulin (IVIG) preparation in chronic inflammatory demyelinating polyneuropathy, the effects of IVIG were investigated using an experimental autoimmune neuropathy model in the rat. IVIG significantly suppressed the progression of neurologic signs and sciatic nerve conduction velocity with the inhibition of inflammatory cell infiltration, mainly of macrophages, to the peripheral nerves. A significant suppressive effect on the expression of macrophage inflammatory protein 1-α (MIP-1α) was simultaneously observed in the nerves. These results suggest that IVIG is effective for inflammatory demyelinating polyneuropathy by inhibiting the chemotactic factor of macrophages.
Assuntos
Quimiocina CCL3/metabolismo , Imunoglobulinas Intravenosas/uso terapêutico , Neurite Autoimune Experimental/tratamento farmacológico , Neurite Autoimune Experimental/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Complexo CD3 , Proteínas de Ligação ao Cálcio/metabolismo , Quimiocina CCL3/genética , Quimiocinas/metabolismo , Modelos Animais de Doenças , Adjuvante de Freund/toxicidade , Masculino , Proteínas dos Microfilamentos/metabolismo , Bainha de Mielina/patologia , Condução Nervosa/efeitos dos fármacos , Neurite Autoimune Experimental/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Tempo de Reação/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia , Fatores de TempoRESUMO
Plasma-derived human antithrombin (pAT) is used for the treatments of disseminated intravascular coagulation (DIC) and hereditary antithrombin deficiencies. We expressed recombinant human antithrombin (rAT) in Chinese hamster ovary (CHO) cells. The purified rAT is composed of 55% alpha-isoform and 45% beta-isoform. The structure of the N-linked oligosaccharides of rAT is the same biantennary complex type as previously found in pAT with less sialylated on the non-reducing ends. Most of the oligosaccharides of rAT are fucosylated at the reducing ends of N-acetylglucosamine, while those of pAT are not fucosylated. Despite of the difference in sialylation and fucosylation of the oligosaccharide units, rAT and pAT showed indistinguishable heparin cofactor and progressive activities, and they bound to thrombin in a one-to-one stoichiometric manner. In lipopolysaccharide (LPS)-induced and thromboplastin-induced DIC rat models, rAT reduced fibrinogen and platelet consumption to a similar extent with pAT. In LPS-induced DIC model, both ATs similarly restrained the increase of alanine aminotransferase and aspartate aminotransferase activities. Finally, pharmacokinetic analysis showed that both ATs had similar half-lives in the circulation of normal rats. Together, the present study demonstrated that rAT prepared in CHO cells has potential for a substitute of pAT in therapeutic use.