Liu L, Törnqvist E, Mattsson P, Eriksson N P, Persson J K, Morgan B P, Aldskogius H, Svensson M
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1995 Sep;68(1):167-79. doi: 10.1016/0306-4522(95)00103-p.
We provide evidence for activation of the complement cascade in the dorsal horn of the spinal cord and in the gracile nucleus in the brainstem following sciatic nerve transection in the adult rat. Immunocytochemical analyses showed immunoreactivity for endogenous immunoglobulin G as shown by immunostaining with F(ab')2 antibodies, as well as complement factors C1, C1q, C3, C3d and C9 in the appropriate central termination areas of the injured sciatic nerve. Results from double labelling immunocytochemistry showed a strong association between immunoglobulin and complement factors on the one hand and reactive microglia on the other. However, some complement immunoreactivity was also found in the neuropil, possibly representing secreted complement. In situ hybridization with an oligonucleotide probe showed a marked increase in C3 messenger RNA, indicating local synthesis of C3 protein. In parallel with activation of complement, there was an increased immunoreactivity for the putative complement inhibitor clusterin, which co-localized with glial fibrillary acidic protein-positive astrocytes. In situ hybridization showed an increased labelling of clusterin messenger RNA. These findings indicate that complement activation and up-regulation of complement inhibitors are prominent central responses to peripheral sensory nerve injury. These responses may therefore be important elements underlying so-called transganglionic degenerative changes in primary sensory axons and terminals.
我们提供了成年大鼠坐骨神经横断后脊髓背角和脑干薄束核中补体级联激活的证据。免疫细胞化学分析显示，用F(ab')2抗体免疫染色表明存在内源性免疫球蛋白G的免疫反应性，以及在受损坐骨神经相应的中枢终末区域存在补体因子C1、C1q、C3、C3d和C9。双重标记免疫细胞化学结果显示，一方面免疫球蛋白和补体因子与另一方面的反应性小胶质细胞之间存在强关联。然而，在神经毡中也发现了一些补体免疫反应性，可能代表分泌的补体。用寡核苷酸探针进行原位杂交显示C3信使核糖核酸显著增加，表明C3蛋白的局部合成。与补体激活同时，假定的补体抑制剂簇蛋白的免疫反应性增加，其与胶质纤维酸性蛋白阳性星形胶质细胞共定位。原位杂交显示簇蛋白信使核糖核酸的标记增加。这些发现表明补体激活和补体抑制剂上调是对周围感觉神经损伤的突出中枢反应。因此，这些反应可能是所谓的初级感觉轴突和终末跨神经节退行性变化的重要潜在因素。
