Figure 2.

Model of LtxA-mediated cell death in monocytes. LtxA preferentially targets CD14⁺ monocytes expressing P2X₇R. Upon treatment with LtxA, monocytes rapidly release ATP into the extracellular milieu, activating P2X₇R. Activation of P2X₇R allows Ca²⁺ to be mobilized, resulting in the clustering of LFA-1 and other β₂ integrins into the lipid raft compartment. LtxA/LFA-1 interaction leads to the activation of caspases. LtxA is internalized in an LFA-1/ β₂ integrin-dependent manner where LtxA is shuttled to the lysosome. LtxA ruptures the lysosomal membrane, allowing leakage of lysosomal proteases, such as Cathepsin D, into the cytosol leading to rapid and irreversible cell death.