Kitoh T, Asai S, Akiyama Y, Kubota M, Mikawa H
Department of Pediatrics, Shin-Kohri Hospital, Hirakata, Japan.
Acta Paediatr Jpn. 1992 Dec;34(6):579-83. doi: 10.1111/j.1442-200x.1992.tb01012.x.
L-Asparaginase has long been used in the treatment of acute lymphoblastic leukemia or malignant lymphoma in childhood. To determine cell type specific sensitivity to this drug, the L-asparaginase-mediated inhibition of blastogenesis of human peripheral T or B lymphocytes was compared. The rate of incorporation of [3H]-thymidine into the DNA of either T lymphocytes due to phytohemagglutinin (PHA) or B lymphocytes due to Staphylococcus aureus Cowan I (SAC) was measured by the addition of Escherichia coli L-asparaginase in the medium. The blastogenic response of either T or B lymphocytes was also determined in medium depleted of exogenous asparagine and/or glutamine, both of which are hydrolyzed by this enzyme. The in vitro blastogenesis of either human T lymphocytes due to PHA or B lymphocytes due to SAC was inhibited by the inclusion of asparaginase in the medium. The deprivation of exogenous asparagine did not have any inhibitory effect on the blastogenic response of both T and B lymphocytes to each mitogen. On the other hand, the glutamine concentration in the culture medium provided a critical influence on the proliferative response of T and B lymphocytes. The rate of incorporation of [3H]-thymidine into DNA was increased markedly as the concentration of glutamine was increased from 2(-7)-2 mmol/l. It is concluded that the mechanism of inhibition of PHA- or SAC-stimulated lymphocyte blastogenesis by L-asparaginase is not asparagine deprivation but glutamine deprivation. Glutamine, which is the most abundant amino acid, is thought to have an important role in the immune response of lymphocytes.
L-天冬酰胺酶长期以来一直用于治疗儿童急性淋巴细胞白血病或恶性淋巴瘤。为了确定细胞类型对这种药物的特异性敏感性，比较了L-天冬酰胺酶介导的对人外周血T或B淋巴细胞增殖的抑制作用。通过在培养基中添加大肠杆菌L-天冬酰胺酶，测量[3H]-胸腺嘧啶核苷掺入因植物血凝素（PHA）刺激的T淋巴细胞或因考恩I型金黄色葡萄球菌（SAC）刺激的B淋巴细胞DNA中的速率。还在缺乏外源性天冬酰胺和/或谷氨酰胺的培养基中测定T或B淋巴细胞的增殖反应，这两种物质都会被这种酶水解。培养基中加入天冬酰胺酶可抑制人T淋巴细胞因PHA或B淋巴细胞因SAC引起的体外增殖。去除外源性天冬酰胺对T和B淋巴细胞对每种有丝分裂原的增殖反应没有任何抑制作用。另一方面，培养基中的谷氨酰胺浓度对T和B淋巴细胞的增殖反应有至关重要的影响。随着谷氨酰胺浓度从2（-7）-2 mmol/L增加，[3H]-胸腺嘧啶核苷掺入DNA的速率显著增加。得出的结论是，L-天冬酰胺酶抑制PHA或SAC刺激的淋巴细胞增殖的机制不是天冬酰胺缺乏，而是谷氨酰胺缺乏。谷氨酰胺是最丰富的氨基酸，被认为在淋巴细胞的免疫反应中起重要作用。
