MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN EXPRESSION ON RAT MICROGLIA FOLLOWING EPIDURAL KAINIC ACID LESIONS
MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN EXPRESSION ON RAT MICROGLIA FOLLOWING EPIDURAL KAINIC ACID LESIONS
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DOI：
10.1002/jnr.490200202
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发表时间：
1988-06-01
影响因子：
4.2
通讯作者：
MCGEER, PL
中科院分区：
文献类型：
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作者：
AKIYAMA, H;ITAGAKI, S;MCGEER, PL
主要组织相容性复合物（MHC）I类和I类表面糖蛋白的表达活跃，观察到反应性小胶质细胞，但不对星形胶质细胞在大鼠脑损伤硬膜外海人酸（KA）诱导的大脑皮层。使用的单克隆抗体是针对MHC I类的OX 18、针对MHC II类的OX 6、针对白细胞共同抗原（LCA）的OX 1和针对泛T淋巴细胞的W3/13。星形胶质细胞用胶质细胞酸性蛋白（GFA）和S100 b蛋白的抗体标记。病变差异影响四个区域：病变的中心区域，大多数细胞死亡;周围区域的病变发生选择性损伤;从病变区域的投影道;和终端领域受损的神经元。在nonlesioned动物，I类表达仅限于血管内皮细胞和一些小的神经胶质细胞。KA处理后，I类阳性圆形细胞在第1天出现在中央区，第5天左右达到高峰，然后缓慢下降。在外周区，I类阳性小胶质细胞从第2天开始出现，它们表现出典型的细胞形态，在某些情况下，它们排列成锥体轮廓包围神经元。反应性小胶质细胞也是I类阳性沿着受损神经元的束和在终端区域。损伤后16-20周，反应降至对照水平，但仍有一些血管内皮细胞和少数圆形细胞在囊性区染色阳性，囊性区是中心区的残余。第1天，II类抗原表达首先以圆形细胞的形式出现在病变的中心区。这些在5-7天达到高峰，此后下降。在第5天的外周区，发现一些阳性的圆形或阿米巴样细胞与典型的反应性小胶质细胞混杂。这种反应在大约1-2周时达到高峰，此后逐渐减少。II类阳性小胶质细胞在第5天出现在纤维束和终末区域，在2-3周后达到高峰，此后下降。I类和II类抗原的双重免疫染色显示，II类阳性细胞明显少于I类阳性细胞，但两组的形态相似。没有星形胶质细胞对I组或II组抗原呈阳性染色。在原发性和继发性病变区，LCA染色观察到的反应性小胶质细胞的表面。在原发性病变中，中心区也有LCA阳性的圆形细胞，但这些细胞在周边区和继发性病变区很少见。LCA与MHC Ⅰ类或Ⅱ类抗原的双重免疫染色显示，LCA阳性细胞大多表达MHC Ⅰ类抗原，少数表达MHC Ⅱ类抗原。这些数据表明，硬膜外KA病变后反应性小胶质细胞大量表达I类和II类抗原。表达这些抗原的细胞似乎来自居民，休息小胶质细胞和血液白细胞，但不是来自星形胶质细胞。
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 surroudning 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 thereafter. 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.