Major histocompatibility complex antigen expression on rat microglia following epidural kainic acid lesions

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Abstract
Vigorous expression of major histocompatibility complex (MHC) class I and class I surface glycoproteins was observed on reactive microglia but not on astrocytes in the rat brain following lesions induced by epidural kainic acid (KA) on the cerebral cortex. The monoclonal antibodies used were OX18 against MHC class I, OX6 against MHC class II, OX1 against leukocyte common antigen (LCA), and W3/13 against pan‐T lymphocytes. Astrocytes were marked by antibodies to glial fibrillary acidic protein (GFA) and S100b protein. The lesion differentially affected four zones: the central area of the lesion where most cells died; the peripheral zone surrounding the lesion where selective damage occurred; projection tracts from the lesioned area; and terminal fields of damaged neurons. In nonlesioned animals, class I expression was confined to vascular endothelial cells and some small glial cells. Following KA treatment, class I‐positive round cells appeared in the central zone at day 1, peaked about day 5, and then slowly declined. In the peripheral zone, class I‐positive microglia were present from day 2 on. They demonstrated classical morphology for such cells, and in some cases arranged themselves in pyramidal profiles surrounding neurons. Reactive microglia were also class I positive along tracts of damaged neurons and in the terminal areas. The reaction was reduced to control levels 16–20 weeks after lesioning although some vascular endothelial cells and a few round cells still stained positively in the cystic area, which was the remnant of the central zone. Class II antigen expression first appeared in the form of round cells in the central zone of the lesion on day 1. These peaked at 5–7 days and declined thereafter. In the peripheral zone on day 5, some positive round or ameboid cells were found intermingled with typical reactive microglia. This reaction peaked at about 1–2 weeks and decreased thereafter. Class II‐positive microglia appeared in fiber tracts and in the terminal areas on day 5, peaked after 2–3 weeks, and declined there‐after. Double immunostaining for class I and II antigens showed that there were significantly fewer class II‐ than class I‐positive cells, but the morphology of the two groups was similar. No astrocytes stained positively for either group I or group II antigen. In both the primary and secondary lesioned areas, LCA staining was observed on the surface of reactive microglia. In the primary lesions there were also LCA‐positive round cells in the central zone, but these were rare in the peripheral zone and the secondary lesioned areas. Double immunostaining for LCA and either class I or class II MHC antigens showed that most LCA positive cells expressed class I antigen, and a few expressed class II antigen. These data demonstrate a considerable expression of both class I and II antigens by reactive microglia following epidural KA lesions. The cells expressing these antigens appeared to be derived from both resident, resting microglia and blood leukocytes, but not from astroglia.