Fig. 8.

Schematic showing the cellular cycle of SOD3 in macrophages. The secreted protein binds to glycosaminoglycans on the cell surface and is internalized via the interaction with LRP1 (1). The internalized SOD3 is sorted and stored in intracellular vesicles of unknown identity (2). Upon stimulation, the macrophage has the capacity to mobilize SOD3 from these vesicles to allow for an acute increase at the cell surface as well as in the surrounding tissue (3). The concomitant expression of NOX2 activity supports the generation of superoxide (O₂^.-) (4). The increased SOD3 activity in the extracellular space has the capacity to modulate the redox environment and affect endocrine and paracrine redox-dependent signaling by generating H₂O₂ as a secondary messenger (5).