Koka Saisudha, Lang Camelia, Niemoeller Olivier M, Boini Krishna M, Nicolay Jan P, Huber Stephan M, Lang Florian
Department of Physiology, University of Tübingen, Germany.
Cell Physiol Biochem. 2008;21(5-6):481-8. doi: 10.1159/000129641. Epub 2008 Apr 24.
Accelerated suicidal death or eryptosis of infected erythrocytes may delay development of parasitemia in malaria. Eryptosis is inhibited by nitric oxide (NO). The present study has been performed to explore, whether inhibition of NO synthase by L-NAME modifies the course of malaria. We show here that L-NAME (>or=10 microM) increased phosphatidylserine exposure of Plasmodium falciparum infected human erythrocytes, an effect significantly more marked than in noninfected human erythrocytes. We further show that parasitemia in Plasmodium berghei infected mice was significantly decreased (from 50% to 18% of circulating erythrocytes 20 days after infection) by addition of 1 mg/ml L-NAME to the drinking water. According to CFSE labelling L-NAME treatment accelerated the clearance of both, noninfected and infected, erythrocytes from circulating blood, but did not significantly extend the life span of infected animals. In conclusion, treatment with L-NAME shortens the life span of circulating erythrocytes and thus delays development of parasitemia during malaria.
加速自杀性死亡或感染红细胞的 eryptosis 可能会延迟疟疾中疟原虫血症的发展。Eryptosis 受到一氧化氮(NO)的抑制。本研究旨在探讨 L-NAME 对 NO 合酶的抑制是否会改变疟疾的病程。我们在此表明,L-NAME(≥10 μM)增加了恶性疟原虫感染的人类红细胞的磷脂酰丝氨酸暴露,这种效应在未感染的人类红细胞中明显更为显著。我们进一步表明,通过在饮用水中添加 1 mg/ml 的 L-NAME,感染伯氏疟原虫的小鼠的疟原虫血症显著降低(感染后 20 天,从循环红细胞的 50%降至 18%)。根据 CFSE 标记,L-NAME 处理加速了循环血液中未感染和感染红细胞的清除,但并未显著延长感染动物的寿命。总之,L-NAME 治疗缩短了循环红细胞的寿命,从而延迟了疟疾期间疟原虫血症的发展。