Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons.

Neuronal Fc-gamma receptor I mediated excitatory effects of IgG immune complex on rat dorsal root ganglion neurons.
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DOI:
10.1016/j.bbi.2011.04.008
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发表时间:
2011-10
影响因子:
15.1
通讯作者:
Ma, Chao
Ma, Chao
中科院分区:
医学1区
文献类型:
--
作者:
Qu, Lintao;Zhang, Pu;LaMotte, Robert H.;Ma, Chao

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疼痛常常伴随抗原特异性免疫相关疾病,但人们对其潜在的神经机制知之甚少。这些疾病的一个共同特征是血清中抗原特异性免疫球蛋白(Ig)G水平升高以及病变组织中存在IgG免疫复合物(IC)。我们假设IC可能直接激活伤害性背根神经节(DRG)神经元中表达的I型Fc -γ受体(FcγRI),并增加神经元兴奋性,从而可能导致疼痛。免疫荧光标记显示,FcγRI(而非FcγRIIB或FcγRIII)在大鼠DRG神经元的一个亚群中表达,包括那些表达伤害性标记的神经元。钙成像显示,IC(而非单独的抗体(IgG)或抗原)可使细胞内钙增加。去除IC中的IgG Fc部分或应用抗 - FcγRI抗体可消除这种效应,这表明FcγRI受体起关键作用。去除细胞外钙或耗尽细胞内钙库可阻止IC诱导的钙反应。在全细胞电流钳记录中,IC使静息膜电位去极化,降低基强度,并增加在2倍基强度的去极化电流诱发的动作电位数量。在约一半的反应性神经元中,IC诱发动作电位发放。这些结果表明,伤害性神经元的一个亚群表达有功能的FcγRI,并且IC对该受体的激活可增加神经元兴奋性。
Pain often accompanies antigen-specific immune-related disorders though little is known of the underlying neural mechanisms. A common feature among these disorders is the elevated level of antigen-specific immunoglobulin (Ig) G in the serum and the presence of IgG immune complex (IC) in the affected tissue. We hypothesize that IC may directly activate the Fc-gamma receptor type I (FcγRI) expressed in nociceptive dorsal root ganglion (DRG) neurons and increase neuronal excitability thus potentially contributing to pain. Immunofluorescent labeling indicated that FcγRI, but not FcγRIIB or FcγRIII, was expressed in a subpopulation of rat DRG neurons including those expressing nociceptive markers. Calcium imaging revealed that the IC, but neither of the antibody (IgG) or antigen alone, produced an increase in intracellular calcium. This effect was abolished by the removal of the IgG Fc portion in the IC or the application of an anti-FcγRI antibody, suggesting a key role of the FcγRI receptor. Removal of extracellular calcium or depletion of intracellular calcium stores prevented the IC-induced calcium response. In whole-cell current-clamp recordings, IC depolarized the resting membrane potential, decreased the rheobase, and increased the number of action potentials evoked by a depolarizing current at 2X rheobase. In about half of the responsive neurons, IC evoked action potential discharges. These results suggest that a subpopulation of nociceptive neurons expresses functional FcγRI and that the activation of this receptor by IC increases neuronal excitability.
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