Ousman S S, David S
Centre for Research in Neuroscience, Montréal General Hospital Research Institute and McGill University, Montréal, Québec, Canada, H3G 1A4.
Glia. 2000 Mar;30(1):92-104.
Lysophosphatidylcholine (LPC) can induce rapid breakdown and removal of myelin from the adult mammalian CNS. In this paper we report the detailed characterization of the immune cell response as well as changes in the expression of cell adhesion molecules and the permeability of the blood-brain barrier after microinjection of LPC into the adult mouse spinal cord. T cells and neutrophils were seen in the spinal cord 6-12 h after LPC injection, but not in PBS-injected mice. Mac-1+ monocytes were also seen at 6 h and 12 h in the white and gray matter of mice injected with LPC and PBS but were significantly greater in the white matter after LPC injections. At later time points LPC induced an increase in the number of activated Mac-1+ macrophages that displayed a variety of morphologies in the white and gray matter. These cells were not present in PBS-injected control mice. LPC also induced widespread microglial activation in the white and gray matter. The number of these Mac-1+ microglia reduced drastically at 96 h after LPC injection suggesting that they may have transformed into Mac-1+ phagocytic cells with a different morphology. These LPC-induced changes in immune cells were accompanied by significant increases in VCAM-1+ and ICAM-1+ blood vessels in the spinal cord. In addition, LPC induced a rapid and widespread disruption of the blood-brain barrier, as compared to PBS injected mice. Therefore, LPC can induce an early and transient T cell and neutrophil response in the CNS. These cells likely promote the rapid influx of monocytes followed by widespread and effective activation of macrophages that mediate rapid phagocytosis of myelin debris.
溶血磷脂酰胆碱（LPC）可诱导成年哺乳动物中枢神经系统（CNS）中的髓鞘迅速分解和清除。在本文中，我们报告了将LPC显微注射到成年小鼠脊髓后免疫细胞反应的详细特征，以及细胞粘附分子表达和血脑屏障通透性的变化。LPC注射后6-12小时在脊髓中可见T细胞和中性粒细胞，而在注射PBS的小鼠中未见。在注射LPC和PBS的小鼠的白质和灰质中，6小时和12小时时也可见Mac-1+单核细胞，但LPC注射后白质中的单核细胞数量显著更多。在随后的时间点，LPC诱导白质和灰质中活化的Mac-1+巨噬细胞数量增加，这些巨噬细胞呈现出多种形态。这些细胞在注射PBS的对照小鼠中不存在。LPC还诱导白质和灰质中广泛的小胶质细胞活化。LPC注射后96小时，这些Mac-1+小胶质细胞的数量急剧减少，这表明它们可能已转变为具有不同形态的Mac-1+吞噬细胞。这些LPC诱导的免疫细胞变化伴随着脊髓中VCAM-1+和ICAM-1+血管的显著增加。此外，与注射PBS的小鼠相比，LPC诱导血脑屏障迅速且广泛的破坏。因此，LPC可在中枢神经系统中诱导早期短暂的T细胞和中性粒细胞反应。这些细胞可能促进单核细胞的快速流入，随后巨噬细胞广泛且有效地活化，介导髓鞘碎片的快速吞噬。
