Lysophosphatidylcholine induces rapid recruitment and activation of macrophages in the adult mouse spinal cord

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.