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Toxins 2013, 5(3), 472-487; doi:10.3390/toxins5030472
Article

P2X Receptor-Dependent Erythrocyte Damage by α-Hemolysin from Escherichia coli Triggers Phagocytosis by THP-1 Cells

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Received: 7 January 2013; in revised form: 6 February 2013 / Accepted: 18 February 2013 / Published: 5 March 2013
(This article belongs to the Special Issue Pore-Forming Toxins)
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Abstract: 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 Ca2+-sensitive K+ (KCa3.1) and Cl channels (TMEM16A) and reduced functions of either of these channels potentiate the HlyA-induced hemolysis. This means that Ca2+-dependent activation of KCa3.1 and TMEM16A protects the cells against early hemolysis. Simultaneous to the HlyA-induced shrinkage, the erythrocytes show increased exposure of phosphatidylserine (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 KCa3.1, which is known to reduce PS-exposure in human erythrocytes subjected to both ionomycin and HlyA. Moreover, we show that 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.
Keywords: phagocytosis; phosphatidyl serine; hemolysin E. coli; monocytes; hemolysis; P2X phagocytosis; phosphatidyl serine; hemolysin E. coli; monocytes; hemolysis; P2X
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Fagerberg, S.K.; Skals, M.; Leipziger, J.; Praetorius, H.A. P2X Receptor-Dependent Erythrocyte Damage by α-Hemolysin from Escherichia coli Triggers Phagocytosis by THP-1 Cells. Toxins 2013, 5, 472-487.

AMA Style

Fagerberg SK, Skals M, Leipziger J, Praetorius HA. P2X Receptor-Dependent Erythrocyte Damage by α-Hemolysin from Escherichia coli Triggers Phagocytosis by THP-1 Cells. Toxins. 2013; 5(3):472-487.

Chicago/Turabian Style

Fagerberg, Steen K.; Skals, Marianne; Leipziger, Jens; Praetorius, Helle A. 2013. "P2X Receptor-Dependent Erythrocyte Damage by α-Hemolysin from Escherichia coli Triggers Phagocytosis by THP-1 Cells." Toxins 5, no. 3: 472-487.



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