Wood A, Wing M G, Benham C D, Compston D A
University of Cambridge, Neurology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
J Neurosci. 1993 Aug;13(8):3319-32. doi: 10.1523/JNEUROSCI.13-08-03319.1993.
Oligodendroglia (ODG) are unique among glial cell types in their capacity to activate complement in the absence of antibody, causing insertion of the potentially damaging membrane attack complex (MAC) into the plasma membrane. Using microfluorimetry of indo-1 fluorescence we have detected a complex oscillatory [Ca2+]i response in ODG following exposure to sublethal dilutions of serum-derived complement. Oscillations were transitory and preceded complete and stable return to resting [Ca2+]i levels, whereas nonoscillating ODG underwent rapid lysis. Depletion of the terminal complement component C9 from serum removed the oscillatory stimulus, which could be restored by reconstitution with purified C9. Exposure to the C9-homologous peptide melittin produced [Ca2+]i oscillations similar in pattern to those induced by whole serum. However, this type of response could not be reproduced by Ca2+ ionophores or mechanical wounding, suggesting that oscillations cannot be provoked by Ca2+ influx alone and depend on the presence of the MAC or a pore-forming lesion. Oscillations were not prevented in the continuous presence of caffeine, demonstrating independence from caffeine-releasable intracellular stores. Inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin produced an abrupt elevation in [Ca2+]i but did not alter the latency between exposure to serum and the initial complement-induced transient. However, the slope of this initial transient was considerably reduced and oscillations suppressed, demonstrating dependence of the oscillatory mechanism on functional endoplasmic reticular Ca2+ stores. The coincidence of ODG recovery with oscillating [Ca2+]i suggests that the complex calcium signal that follows MAC attack may stimulate repair or protective mechanisms.
少突胶质细胞（ODG）在胶质细胞类型中独具特色，能够在无抗体的情况下激活补体，致使具有潜在破坏性的膜攻击复合物（MAC）插入质膜。通过indo-1荧光的微荧光测定法，我们检测到在暴露于血清来源补体的亚致死稀释液后，少突胶质细胞中出现复杂的振荡性[Ca2+]i反应。振荡是短暂的，在完全且稳定地恢复到静息[Ca2+]i水平之前出现，而无振荡的少突胶质细胞则迅速裂解。从血清中去除末端补体成分C9消除了振荡刺激，通过用纯化的C9重构可恢复该刺激。暴露于C9同源肽蜂毒素产生的[Ca2+]i振荡模式与全血清诱导的振荡相似。然而，这种类型的反应不能由Ca2+离子载体或机械损伤重现，这表明振荡不能仅由Ca2+内流引发，而是依赖于MAC或成孔损伤的存在。在持续存在咖啡因的情况下，振荡并未受到阻止，这表明其独立于咖啡因可释放的细胞内储存。用毒胡萝卜素抑制内质网Ca(2+)-ATPase会使[Ca2+]i突然升高，但不会改变暴露于血清与补体诱导的初始瞬变之间的延迟。然而，这个初始瞬变的斜率显著降低，振荡受到抑制，这表明振荡机制依赖于功能性内质网Ca2+储存。少突胶质细胞的恢复与振荡性[Ca2+]i的巧合表明，MAC攻击后出现的复杂钙信号可能刺激修复或保护机制。
