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P2X receptor‐dependent erythrocyte damage by α‐hemolysin from Escherichia coli triggers phagocytosis by THP‐1 cells
Author(s) -
Fagerberg Steen K,
Skals Marianne,
Leipziger Jens,
Praetorius Helle A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb888
Subject(s) - phagocytosis , hemolysin , haemolysis , hemolysis , phagosome , chemistry , lysis , red blood cell , microbiology and biotechnology , biology , biochemistry , immunology , virulence , gene
The pore‐forming exotoxin α‐hemolysin from E. coli causes a significant volume reduction of human erythrocytes that precedes the ultimate swelling and lysis. This shrinkage results from activation of Ca 2+ ‐sensitive K + (K Ca 3.1) and Cl − channels (TMEM16A) and reduced functions of both of these channels potentiate the HlyA‐induced haemolysis. This means that Ca 2+‐ dependent activation of K Ca 3.1 and TMEM16A protects the cells against early haemolysis. Simultaneous to the HlyA‐induced shrinkage the erythrocytes show increased exposure of phosphatidyl‐serine (PS) in the outer plasma membrane leaflet, which is known to be a keen trigger for phagocytosis. We hypothesize that exposure to HlyA elicits removal of the damaged erythrocytes by phagocytic cells. Cultured THP‐1 cells as a model for erythrocytal phagocytosis was verified by a variety of methods including live cell imaging. We consistently found the HlyA to very potently trigger phagocytosis of erythrocytes by THP‐1 cells. The HlyA‐induced phagocytosis was prevented by inhibition of K Ca 3.1, which is known to reduce PS‐exposure in human erythrocytes exposed to both ionomycin and HlyA. Moreover, we show that the P2X receptor inhibition, which prevents the cell damages caused by HlyA, also reduced that HlyA‐induced PS‐exposure and phagocytosis. Based on these results, we propose that erythrocytes, damaged by HlyA‐insertion, are effectively cleared from the blood stream. This mechanism will potentially reduce the risk of intravascular hemolysis