Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure. Issue 13 (28th May 2020)

• Record Type: Journal Article
• Authors: Geng, Zhijun; Huang, Jing; Kang, Lin; Gao, Shan; Yuan, Yuan; Li, Yanwei; Wang, Jing; Xin, Wenwen; Wang, Jinglin
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 13(2020)
• Page Start: 7341
• Page End: 7352
• Publication Date: 2020-05-28
• Subjects: ceramide -- epsilon toxin -- haemolysis -- human erythroleukaemia cell line -- myelin and lymphocyte receptor -- phosphatidylserine; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15315
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Epsilon toxin (ETX) is a 33‐kDa pore‐forming toxin produced by type B and D strains of Clostridium perfringens . We previously found that ETX caused haemolysis of human red blood cells, but not of erythrocytes from other species. The cellular and molecular mechanisms of ETX‐mediated haemolysis are not well understood. Here, we investigated the effects of ETX on erythrocyte volume and the role of the putative myelin and lymphocyte (MAL) receptors in ETX‐mediated haemolysis. We observed that ETX initially decreased erythrocyte size, followed by a gradual increase in volume until lysis. Moreover, ETX triggered phosphatidylserine (PS) exposure and enhanced ceramide abundance in erythrocytes. Cell shrinkage, PS exposure and enhanced ceramide abundance were preceded by increases in intracellular Ca 2+ concentration. Interestingly, lentivirus‐mediated RNA interference studies in the human erythroleukaemia cell line (HEL) cells confirmed that MAL contributes to ETX‐induced cytotoxicity. Additionally, ETX was shown to bind to MAL in vitro. The results of this study recommend that ETX‐mediated haemolysis is associated with MAL receptor activation in human erythrocytes. These data imply that interventions affecting local MAL‐mediated autocrine and paracrine signalling may prevent ETX‐mediated erythrocyte damage.