Wang Kan, Mahmud Hasan, Föller Michael, Biswas Raja, Lang Karl S, Bohn Erwin, Götz Friedrich, Lang Florian
Department of Physiology, University of Tübingen, Tübingen, , Germany.
Cell Physiol Biochem. 2008;22(5-6):381-6. doi: 10.1159/000187116. Epub 2008 Dec 11.
Sepsis is paralleled by anemia, an effect partially resulting from eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Pathogen-induced eryptosis may partially result from interaction of bacterial cell wall components such as lipoproteins with the erythrocyte cell membrane. The present study explored, whether the synthetic lipopeptide Pam3CSK4 mimicking the acylated amino terminus of bacterial lipoproteins triggers eryptosis. According to annexin-V-binding in FACS analysis, Pam3CSK4 (1 microg/ml) stimulated phosphatidylserine exposure, an effect significantly blunted in the nominal absence of Ca(2+). According to Fluo3 fluorescence, Pam3CSK4 increased cytosolic Ca(2+) activity and moderately stimulated erythrocytic ceramide formation, both major triggers of eryptosis. In conclusion, bacterial lipoproteins participate in the stimulation of erythrocyte cell membrane scrambling by bacterial cell wall components. Thus, lipoprotein-dependent suicidal erythrocyte death may contribute to the pleotropic effects of sepsis.
脓毒症常伴有贫血，这种效应部分源于红细胞的自杀性死亡——红细胞凋亡。红细胞凋亡的特征是细胞膜磷脂酰丝氨酸外翻。病原体诱导的红细胞凋亡可能部分源于细菌细胞壁成分（如脂蛋白）与红细胞膜的相互作用。本研究探讨了模拟细菌脂蛋白酰化氨基末端的合成脂肽Pam3CSK4是否会引发红细胞凋亡。根据流式细胞术分析中的膜联蛋白-V结合情况，Pam3CSK4（1微克/毫升）刺激了磷脂酰丝氨酸的暴露，在名义上无Ca(2+)的情况下，这种效应明显减弱。根据Fluo3荧光分析，Pam3CSK4增加了胞质Ca(2+)活性，并适度刺激了红细胞神经酰胺的形成，这两者都是红细胞凋亡的主要触发因素。总之，细菌脂蛋白参与了细菌细胞壁成分对红细胞膜磷脂酰丝氨酸外翻的刺激。因此，脂蛋白依赖性红细胞自杀性死亡可能导致脓毒症的多效性效应。
