Leukotoxin from Aggregatibacter actinomycetemcomitans causes shrinkage and P2X receptor-dependent lysis of human erythrocytes.
| Autor: | Munksgaard PS; Department of Biomedicine, Health, Aarhus University, Denmark., Vorup-Jensen T, Reinholdt J, Söderström CM, Poulsen K, Leipziger J, Praetorius HA, Skals M |
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| Jazyk: | angličtina |
| Zdroj: | Cellular microbiology [Cell Microbiol] 2012 Dec; Vol. 14 (12), pp. 1904-20. Date of Electronic Publication: 2012 Sep 25. |
| DOI: | 10.1111/cmi.12021 |
| Abstrakt: | Leukotoxin (LtxA) is a virulence factor secreted by the bacterium Aggregatibacter actinomycetemcomitans, which can cause localized aggressive periodontitis and endocarditis. LtxA belongs to the repeat-in-toxin (RTX) family of exotoxins of which other members inflict lysis by formation of membrane pores. Recently, we documented that the haemolytic process induced by another RTX toxin [α-haemolysin (HlyA) from Escherichia coli] requires P2X receptor activation and consists of sequential cell shrinkage and swelling. In contrast, the cellular and molecular mechanisms of LtxA-mediated haemolysis are not fully understood. Here, we investigate the effect of LtxA on erythrocyte volume and whether P2 receptors also play a part in LtxA-mediated haemolysis. We observed that LtxA initially decreases the cell size, followed by a gradual rise in volume until the cell finally lyses. Moreover, LtxA triggers phosphatidylserine (PS) exposure in the erythrocyte membrane and both the shrinkage and the PS-exposure is preceded by increments in the intracellular Ca(2+) concentration ([Ca(2+)](i)). Interestingly, LtxA-mediated haemolysis is significantly potentiated by ATP release and P2X receptor activation in human erythrocytes. Furthermore, the LtxA-induced [Ca(2+)](i) increase and following volume changes partially depend on P2 receptor activation. Theseobservations imply that intervention against local P2-mediated auto- and paracrine signalling may prevent LtxA-mediated cell damage. (© 2012 Blackwell Publishing Ltd.) |
| Databáze: | MEDLINE |
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