Nygaard Unni Cecilie, Aase Audun, Løvik Martinus
Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
BMC Immunol. 2005 Jun 21;6:11. doi: 10.1186/1471-2172-6-11.
There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated) and IgG2a (Th1-associated) responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP) affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA), after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-gamma and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN) five days after injection of OVA and PSP separately or in combination was determined.
PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-gamma levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-gamma in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only).
Genetic factors (i.e. the strain of mice) influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that the ex vivo cytokine patterns did not predict the in vivo Th2- and Th1-associated antibody response patterns in the different mouse strains. The results indicate that insoluble particles act by increasing the inherent response to the allergen, and that the genetic background may determine whether an additional Th1-associated component is added to the response.
越来越多的流行病学和实验证据表明,空气中的颗粒物污染会加重哮喘和过敏症状,在较小程度上也会加重过敏致敏。遗传因素似乎不仅会影响颗粒物对过敏原特异性IgE(与Th2相关)和IgG2a(与Th1相关)反应的佐剂效应的程度,还会影响其性质。在本研究中,我们旨在调查遗传背景如何影响对单独及联合使用的过敏原和颗粒物的反应。我们研究了将聚苯乙烯颗粒(PSP)皮下注射到BALB/cA、BALB/cJ、NIH和C3H/HeN小鼠的足垫后,其对针对模型过敏原卵清蛋白(OVA)的IgE和IgG2a反应有何影响。此外,还测定了在分别或联合注射OVA和PSP五天后,来自引流腘窝淋巴结(PLN)的经伴刀豆球蛋白A刺激的细胞的离体IL-4、IFN-γ和IL-10细胞因子分泌情况。
与OVA一起注射的PSP增加了所有检测品系中OVA特异性IgE抗体的水平。相比之下,仅在NIH和C3H/HeN小鼠中IgG2a水平显著升高。在OVA存在的情况下,PSP增加了BALB/cA、NIH和C3H/HeN小鼠中的细胞数量以及IL-4、IL-10和IFN-γ水平,但NIH小鼠中的IFN-γ除外。然而,每个小鼠品系对OVA+PSP、OVA和PSP都有其独特的反应模式,并且也有其独特的背景细胞因子反应(即仅注射缓冲液的小鼠细胞中的细胞因子反应)。
遗传因素(即小鼠品系)影响了PSP对淋巴结中二次抗体反应和初次细胞反应的佐剂效应的易感性,以及对单独给予的OVA和PSP的细胞反应。有趣的是,单独的PSP在一些小鼠品系中诱导了淋巴结中的细胞因子反应。此外,我们发现离体细胞因子模式并不能预测不同小鼠品系中的体内Th2和Th1相关抗体反应模式。结果表明,不溶性颗粒通过增加对过敏原的固有反应起作用,并且遗传背景可能决定是否会在反应中添加额外的Th1相关成分。