Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil.
Int Immunopharmacol. 2013 Aug;16(4):436-43. doi: 10.1016/j.intimp.2013.04.019. Epub 2013 May 2.
Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25mg/kg) and AMPH (2.0mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801+AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice.
谷氨酸在中枢神经系统（CNS）中充当神经递质，并调节免疫细胞的活性。在淋巴细胞中，NMDA 谷氨酸受体调节细胞内钙、活性氧物质的产生和细胞因子的合成。MK-801 是一种 NMDA 受体开放通道阻断剂，可抑制肥大细胞内钙离子的进入，从而防止肥大细胞脱颗粒。有几条证据表明 NMDA 谷氨酸受体参与了安非他命（AMPH）诱导的作用。据报道，AMPH 处理可改变过敏性肺炎症。本研究评估了 MK-801（0.25mg/kg）和 AMPH（2.0mg/kg）单独或联合给药对致敏和激发的小鼠过敏性肺炎症的影响，以及 NMDA 受体在这一过程中的可能参与。在 OVA 致敏和激发的小鼠中，AMPH 和 MK-801 单独给药可减少细胞向肺部迁移，减少 BAL 上清液中 IL-13 和 IL10 的水平，减少 BAL 中粒细胞中 ICAM-1 和 L-选择素的表达，并减少肥大细胞脱颗粒。AMPH 处理还降低了 IL-5 的水平。当两种药物同时给药时，MK-801 逆转了 AMPH 对 OVA 致敏和激发的小鼠 BAL 中嗜酸性粒细胞和中性粒细胞数量的减少，以及对粒细胞中 L-选择素和 ICAM-1 表达、BAL 上清液中 IL-10、IL-5 和 IL-13 水平的影响，并增加了肥大细胞脱颗粒。同时，MK-801、AMPH 或 MK-801+AMPH 治疗增加了过敏小鼠的血清皮质酮水平。这些结果是根据 AMPH 和 MK-801 通过中枢神经系统（即 HPA 轴活性）到外周的内分泌流出的可能间接作用来讨论的，或者是由于这些药物对免疫细胞活性的直接作用，强调了肥大细胞参与了小鼠的过敏性肺反应。
