Open AccessClostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure
Author(s) -
Geng Zhijun,
Huang Jing,
Kang Lin,
Gao Shan,
Yuan Yuan,
Li Yanwei,
Wang Jing,
Xin Wenwen,
Wang Jinglin
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15315
Subject(s) - haemolysis , clostridium perfringens , cytolysis , biology , phosphatidylserine , toxin , cytotoxicity , receptor , hemolysis , cytolysin , microbiology and biotechnology , in vitro , biochemistry , chemistry , immunology , phospholipid , genetics , membrane , virulence , bacteria , gene
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.