The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid

被引:82
作者
Dreyer, EB
Lipton, SA
机构
[1] HARVARD UNIV,CHILDRENS HOSP,SCH MED,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA 02115
[2] HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB,BOSTON,MA
[3] HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115
[4] HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115
[5] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115
[6] HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115
[7] HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115
[8] HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA
关键词
excitotoxicity; AIDS; rat model; phospholipase A(2); HIV-1 envelope protein;
D O I
10.1111/j.1460-9568.1995.tb01048.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The human immunodeficiency virus coat protein gp120 injures central mammalian neurons both in vitro and in vivo, and this observation may contribute, at least in part, to the neurological dysfunction associated with the acquired immunodeficiency syndrome. Recent work suggests that gp120 mediates neuronal damage predominantly via an indirect route involving activation of brain macrophages. We have previously shown that the stimulation of N-methyl-D-aspartate receptors by excitatory amino acids is essential for the neuronal injury observed with gp120. Here we show that gp120 impairs astrocyte uptake of excitatory amino acids and the excess glutamate thus engendered may contribute to the increased neuronal damage. We also studied the mechanism whereby gp120 inhibits the uptake of excitatory amino acids by astrocytes. We present data suggesting that at least one pathway involves a direct effect of gp120 on macrophages, which in turn release arachidonic acid, a known inhibitor of excitatory amino acid uptake by astrocytes. Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages.
引用
收藏
页码:2502 / 2507
页数:6
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