Liu L, Persson J K, Svensson M, Aldskogius H
Department of Anatomy, Biomedical Center, Uppsala University, Sweden.
Glia. 1998 Jul;23(3):221-38.
We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.
我们研究了中枢神经系统沃勒变性过程中的胶质细胞反应、与补体级联相关化合物的可能表达，包括假定的补体抑制剂簇集素，以及它们的细胞关联。对增殖模式的检查显示，神经根切断术后有总体上更强的有丝分裂活性，外周神经损伤后小胶质细胞在这种增殖中起唯一作用，但此外，神经根切断术后还有一小部分增殖的星形胶质细胞。用吞噬细胞标志物ED1进行免疫染色在神经根切断术后逐渐变得非常明显，这可能反映了对广泛神经纤维崩解的一种反应。腰背部背根切断术未在脊髓背角、背索或薄束核中诱导内源性免疫球蛋白G（IgG）沉积或补体表达。这与外周神经损伤后的情况形成显著对比，外周神经损伤似乎激活了中枢感觉突附近的整个补体级联反应。簇集素是一种具有补体抑制作用的多功能蛋白，在星形胶质细胞的背索中显著上调。此外，在少突胶质细胞的变性白质中有强烈的簇集素表达诱导，这可能反映了这些细胞中的变性过程。这些发现表明：1）小胶质细胞的补体表达与IgG沉积密切相关；2）轴突切断的神经元胞体，而非变性的中枢纤维，会发生诱导这种沉积的变化；3）簇集素与神经元损伤后的补体表达无关，但在沃勒变性过程中参与调节少突胶质细胞的状态。
