Fig. 3.

Model for leukotoxin from Aggregatibacter (LtxA)-induced haemolysis. 1 Interaction between LtxA and the erythrocyte membrane leads to an influx of ions and increase in [Ca²⁺]_i. 2 The increase in [Ca²⁺]_i stimulates a Ca²⁺-activated K⁺ efflux mediated by the Ca²⁺-activated K⁺ channel, KCa3.1. K⁺–Cl⁻ co-transporters (KCCs) contribute to the K⁺ efflux. Initially, the K⁺ efflux exceeds the influx of ions leading to osmotically obliged H₂O efflux and volume reduction. ATP is released from the cell through a yet unknown pathway and activates P2X receptors on the erythrocyte membrane, which is required for the full haemolytic effect of LtxA. In addition, activation of pannexin channels is also necessary for LtxA-induced haemolysis. 3 Later, the influx of ions exceeds the efflux of K⁺ resulting in osmotically obliged H₂O influx and cell swelling. Finally, the erythrocyte lyses. (Reproduced from [121] with permission from John Wiley and Sons.)