Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-leucine methyl ester by monocytes or polymorphonuclear leukocytes.
Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-leucine methyl ester by monocytes or polymorphonuclear leukocytes.
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溶酶体酶活性产物对细胞功能的调节：单核细胞或多形核白细胞通过 L-亮氨酸甲酯产生的二肽甲酯消除人类自然杀伤细胞。
DOI：
10.1073/pnas.82.8.2468
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发表时间：
1985
影响因子：
11.1
通讯作者：
Lipsky,PE
中科院分区：
文献类型：
--
作者：
Thiele,DL;Lipsky,PE
L-亮氨酸甲酯（Leu-OMe）是一种亲溶酶体化合物，可不可逆地去除人外周血单核细胞的自然杀伤细胞（NK）功能。这种效应依赖于单核吞噬细胞（M phi）或多形核白细胞（PMN）的存在，并被溶酶体抑制剂如氯喹或NH 4Cl阻止。当M phi或PMN与Leu-OMe孵育时，形成了一种产物，其消除了混合淋巴细胞群的所有NK功能。这种作用不需要M phi或PMN的存在，也不受溶酶体酶抑制剂的抑制。薄层层析和质谱分析表明，该NK毒性产物为L-亮氨酰-L-亮氨酸甲酯（Leu-Leu-OMe）。当人淋巴细胞暴露于大于50 μ M的Leu-Leu-OMe 15分钟时，所有NK功能都被不可逆地消除。其他含有非极性L氨基酸的二肽甲酯引起类似的效果，但取代含有极性或带电侧链的氨基酸或D立体异构体产生的化合物，对NK没有毒性作用。这些结果表明，M phi和PMN可以通过释放二肽缩合产物Leu-Leu-OMe通过溶酶体介导的机制产生的Leu-Leu-OMe调节NK功能。这些数据表明，溶酶体酶活性的特定产物可能对邻近细胞的功能具有强有力的影响。
L-Leucine methyl ester (Leu-OMe) is a lysosomotropic compound that irreversibly removes natural killer cell (NK) function from human peripheral blood mononuclear cells. This effect was dependent on the presence of mononuclear phagocytes (M phi) or polymorphonuclear leukocytes (PMN) and was prevented by lysosomal inhibitors such as chloroquine or NH4Cl. When M phi or PMN were incubated with Leu-OMe, a product was formed that eliminated all NK function from mixed lymphocyte populations. This effect did not require the presence of M phi or PMN and was not prevented by lysosomal enzyme inhibitors. Thin-layer chromatography and mass spectral analysis revealed that this NK-toxic product was L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). When human lymphocytes were exposed to greater than 50 microM Leu-Leu-OMe for 15 min, all NK function was irreversibly eliminated. Other dipeptide methyl esters containing nonpolar L amino acids caused similar effects, but substitution with amino acids containing polar or charged side chains or with D stereoisomers produced compounds that had no toxic effect on NK. These findings indicate that M phi and PMN can regulate NK function by releasing the dipeptide condensation product Leu-Leu-OMe generated from Leu-OMe via a lysosomally mediated mechanism. The data show that specific products of lysosomal enzyme activity may have potent effects on the function of adjacent cells.