Martinsson K, Hultman P
Division of Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linkoping University, SE-581 85 Linkoping, Sweden.
Clin Exp Immunol. 2006 May;144(2):309-18. doi: 10.1111/j.1365-2249.2006.03057.x.
Inorganic mercury (Hg) in genetically susceptible mouse strains induces a T cell-dependent, systemic autoimmune condition (HgIA) characterized by immunostimulation, anti-nuclear antibodies (ANA) and systemic immune-complex (IC) deposits. The exact phenotypic expression of HgIA in different strains depends on H-2 and non-H-2 genes. Fc receptors (FcRs) are important in the development of many autoimmune diseases. In this study, the effect of targeted mutations for activating and inhibiting FcRs in the BALB/c model of HgIA was examined. Hg-treated BALB/c mice without mutation (wild-type, wt) showed heavy IC deposits in the renal glomerular mesangium, as well as in renal and splenic vessel walls. The renal mesangial IC deposits were severely reduced in Hg-treated BALB/c mice without the gamma-chain (lack of the activating receptors FcgammaRI, FcgammaRIII and FcinRI), but unchanged in mice lacking the inhibitory FcgammaRIIB. The Hg-induced vessel wall IC deposits present in wt mice were abolished and reduced in the FcRgamma and FcgammaRIIB strains, respectively. Hg-treated BALB/c wt mice and mice without the gamma-chain showed an increase in serum IgE, while the increase in IgG1 was attenuated in the latter strain. In contrast, absence of the inhibiting FcgammaRIIB augmented the Hg-induced increase of both serum IgG1 and IgE. In conclusion, FcRs are important mainly for the induction of systmeic IC deposits in the HgIA model, but also affects serum IgG1 and IgE levels.
在基因易感小鼠品系中，无机汞（Hg）会诱发一种T细胞依赖性的全身性自身免疫病症（汞诱导自身免疫病，HgIA），其特征为免疫刺激、抗核抗体（ANA）以及全身性免疫复合物（IC）沉积。HgIA在不同品系中的具体表型表达取决于H-2和非H-2基因。Fc受体（FcRs）在许多自身免疫性疾病的发展过程中起着重要作用。在本研究中，检测了在HgIA的BALB/c模型中激活和抑制FcRs的靶向突变的影响。未发生突变的经Hg处理的BALB/c小鼠（野生型，wt）在肾小球系膜以及肾和脾血管壁中显示出大量IC沉积。在没有γ链的经Hg处理的BALB/c小鼠（缺乏激活受体FcγRI、FcγRIII和FcinRI）中，肾系膜IC沉积显著减少，但在缺乏抑制性FcγRIIB的小鼠中则无变化。野生型小鼠中存在的Hg诱导的血管壁IC沉积在FcRγ和FcγRIIB品系中分别被消除和减少。经Hg处理的BALB/c野生型小鼠和没有γ链的小鼠血清IgE增加，而在后者品系中IgG1的增加则减弱。相反，缺乏抑制性FcγRIIB会增强Hg诱导的血清IgG1和IgE的增加。总之，FcRs主要对HgIA模型中全身性IC沉积的诱导很重要，但也会影响血清IgG1和IgE水平。
