P2X7 receptors mediate resistance to toxin-induced cell lysis.
In the majority of cells, the integrity of the plasmalemma is recurrently compromised by mechanical or chemical stress. Serum complement or bacterial pore-forming toxins can perforate the plasma membrane provoking uncontrolled Ca(2+) influx, loss of cytoplasmic constituents and cell lysis. Plasmalemmal blebbing has previously been shown to protect cells against bacterial pore-forming toxins. The activation of the P2X7 receptor (P2X7R), an ATP-gated trimeric membrane cation channel, triggers Ca(2+) influx and induces blebbing. We have investigated the role of the P2X7R as a regulator of plasmalemmal protection after toxin-induced membrane perforation caused by bacterial streptolysin O (SLO). Our results show that the expression and activation of the P2X7R furnishes cells with an increased chance of surviving attacks by SLO. This protective effect can be demonstrated not only in human embryonic kidney 293 (HEK) cells transfected with the P2X7R, but also in human mast cells (HMC-1), which express the receptor endogenously. In addition, this effect is abolished by treatment with blebbistatin or A-438079, a selective P2X7R antagonist. Thus blebbing, which is elicited by the ATP-mediated, paracrine activation of the P2X7R, is part of a cellular non-immune defense mechanism. It pre-empts plasmalemmal damage and promotes cellular survival. This mechanism is of considerable importance for cells of the immune system which carry the P2X7R and which are specifically exposed to toxin attacks.
Institute of Anatomy, University of Bern, Bern, Switzerland.
Roman
R
Schoenauer
Institute of Anatomy, University of Bern, Bern, Switzerland.
Alexander P
AP
Atanassoff
Institute of Anatomy, University of Bern, Bern, Switzerland.
Heidi
H
Wolfmeier
Inflammation and Experimental Surgery Research, University Hospital Virgen de la Arrixaca - FFIS, Murcia, Spain.
Pablo
P
Pelegrin
Institute of Anatomy, University of Bern, Bern, Switzerland.
Eduard B
EB
Babiychuk
Institute of Anatomy, University of Bern, Bern, Switzerland. Electronic address: annette.draeger@ana.unibe.ch.
Annette
A
Draeger
D001426:Bacterial Proteins / Q000633:toxicity; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D016133:Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000502:physiology*; D013301:Streptolysins / Q000633:toxicity*
D001426:Bacterial Proteins; D017931:DNA Primers; D058486:Receptors, Purinergic P2X7; D013301:Streptolysins; C025964:streptolysin O
Annexin; Blebbing; Calcium; Lysis; P2X7; Plasmalemma