Lang Florian, Lang Philipp A, Lang Karl S, Brand Verena, Tanneur Valerie, Duranton Christophe, Wieder Thomas, Huber Stephan M
Physiologisches Institut der Universität Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Pflugers Arch. 2004 Jun;448(3):319-24. doi: 10.1007/s00424-004-1254-9. Epub 2004 Mar 20.
Infection of erythrocytes by the malaria pathogen Plasmodium falciparum leads to activation of several distinct anion channels and a non-selective, Ca2+-permeable cation channel. All channel types are presumably activated by the oxidative stress generated by the pathogen. Similar or identical channels are activated by oxidation of non-infected erythrocytes. Activation of the non-selective cation channel allows entry of Ca2+ and Na+, both of which are required for intracellular growth of the pathogen. The entry of Ca2+ stimulates an intraerythrocytic scramblase that facilitates bi-directional phospholipid migration across the bilayer, resulting in breakdown of the phosphatidylserine asymmetry of the cell membrane. The exposure of phosphatidylserine at the outer surface of the cell membrane is presumably followed by binding to phosphatidylserine receptors on macrophages and subsequent phagocytosis of the affected erythrocyte. The lysosomal degradation may eventually eliminate the pathogen. The channel may thus play a dual role in pathogen survival. Absence of the channels is not compatible with pathogen growth, enhanced channel activity accelerates erythrocyte "apoptosis" that may represent a host defence mechanism serving to eliminate infected erythrocytes.
疟原虫恶性疟原虫感染红细胞会导致几种不同的阴离子通道以及一种非选择性、Ca2+ 可渗透的阳离子通道被激活。所有这些通道类型可能都是由病原体产生的氧化应激所激活的。未感染的红细胞被氧化时也会激活相似或相同的通道。非选择性阳离子通道的激活使得 Ca2+ 和 Na+ 进入细胞，这两者都是病原体在细胞内生长所必需的。Ca2+ 的进入会刺激红细胞内的磷脂翻转酶，促进磷脂在双分子层间的双向迁移，导致细胞膜磷脂酰丝氨酸不对称性的破坏。细胞膜外表面磷脂酰丝氨酸的暴露可能随后会与巨噬细胞上的磷脂酰丝氨酸受体结合，接着受影响的红细胞会被吞噬。溶酶体降解最终可能会清除病原体。因此，该通道可能在病原体存活中发挥双重作用。通道缺失与病原体生长不相容，通道活性增强会加速红细胞“凋亡”，这可能是一种宿主防御机制，用于清除被感染的红细胞。
