Fig. 8.

Size-dependent toxicity of submicron immunoglobulin particles on endothelial cells. (A) the diagram illustrates the formation of spherical IVIG particles using SiMP core particles, ranging in size from 200 nm to 2 μm. The diagram also highlights several key aspects of submicron IVIG particle toxicity. (B) Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Interestingly, the toxicity of submicron IVIG-SiMPs only in TNFα-stimulated- but not in unstimulated endothelial cells. (C) The effect is associated with multiple cellular responses, including apoptosis induction mTOR-dependent activation of autophagy, mitophagy and the release of extracellular vesicle (EV). Moreover, (D) Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation