Next Article in Journal
Diversity of Pea-Associated F. proliferatum and F. verticillioides Populations Revealed by FUM1 Sequence Analysis and Fumonisin Biosynthesis
Next Article in Special Issue
More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins
Previous Article in Journal
Effect of Gating Modifier Toxins on Membrane Thickness: Implications for Toxin Effect on Gramicidin and Mechanosensitive Channels
Article Menu

Export Article

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

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

Department of Biomedicine, Physiology, Aarhus University, Ole Worms Allé 4, 8000 Aarhus C, Building 1160, Aarhus 8000, Denmark
*
Author to whom correspondence should be addressed.
Received: 7 January 2013 / Revised: 6 February 2013 / Accepted: 18 February 2013 / Published: 5 March 2013
(This article belongs to the Special Issue Pore-Forming Toxins)
View Full-Text   |   Download PDF [826 KB, uploaded 5 March 2013]   |  

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 (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top