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花生过敏原DNA免疫小鼠后,菌株依赖性诱导过敏致敏反应。

Strain-dependent induction of allergic sensitization caused by peanut allergen DNA immunization in mice.

作者信息

Li X, Huang C K, Schofield B H, Burks A W, Bannon G A, Kim K H, Huang S K, Sampson H A

机构信息

Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.

出版信息

J Immunol. 1999 Mar 1;162(5):3045-52.

Abstract

To investigate the potential application of allergen gene immunization in the modulation of food allergy, C3H/HeSn (C3H) mice received i.m. injections of pAra h2 plasmid DNA encoding one of the major peanut allergens, Ara h2. Three weeks following pDNA immunization, serum Ara h2-specific IgG2a, IgG1, but not IgE, were increased significantly in a dose-dependent manner. IgG1 was 30-fold higher in multiply compared with singly immunized mice. Ara h2 or peanut protein injection of immunized mice induced anaphylactic reactions, which were more severe in multiply immunized mice. Heat-inactivated immune serum induced passive cutaneous anaphylaxis, suggesting that anaphylaxis in C3H mice was mediated by IgG1. IgG1 responses were also induced by intradermal injection of pAra h2, and by i.m. injection of pOMC, the plasmid DNA encoding the major egg allergen protein, ovomucoid. To elucidate whether the pDNA immunization-induced anaphylaxis was a strain-dependent phenomenon, AKR/J and BALB/c mice also received multiple i.m. pAra h2 immunizations. Injection of peanut protein into these strains at weeks 3 or 5 following immunization did not induce reactions. Although IgG2a was increased significantly from week 2 in AKR/J mice and from week 4 in BALB/c mice and remained elevated for at least 6 wk, no IgG1 or IgE was detected. These results indicate that the type of immune responses to pDNA immunization in mice is strain dependent. Consequently, models for studying human allergen gene immunization require careful selection of suitable strains. In addition, this suggests that similar interindividual variation is likely in humans.

摘要

为研究变应原基因免疫在调节食物过敏中的潜在应用,C3H/HeSn(C3H)小鼠接受了肌肉注射编码主要花生变应原之一Ara h2的pAra h2质粒DNA。在注射pDNA免疫三周后,血清中Ara h2特异性IgG2a、IgG1显著增加,呈剂量依赖性,但IgE未增加。多次免疫小鼠的IgG1比单次免疫小鼠高30倍。给免疫小鼠注射Ara h2或花生蛋白可诱发过敏反应,多次免疫小鼠的反应更严重。热灭活免疫血清可诱发被动皮肤过敏反应,提示C3H小鼠的过敏反应由IgG1介导。皮内注射pAra h2以及肌肉注射编码主要鸡蛋变应原蛋白卵类粘蛋白的质粒DNA pOMC也可诱导IgG1反应。为阐明pDNA免疫诱导的过敏反应是否为品系依赖性现象,AKR/J和BALB/c小鼠也接受了多次肌肉注射pAra h2免疫。在免疫后第3周或第5周给这些品系注射花生蛋白未诱发反应。虽然AKR/J小鼠从第2周起、BALB/c小鼠从第4周起IgG2a显著增加并至少持续升高6周,但未检测到IgG1或IgE。这些结果表明小鼠对pDNA免疫的免疫反应类型具有品系依赖性。因此,研究人类变应原基因免疫的模型需要仔细选择合适的品系。此外,这表明人类中可能也存在类似的个体间差异。

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