Podocytes as novel sources of neutrophil serine proteases: expression and regulation by inflammatory molecular patterns

Podocytes are essential components of the glomerular filtration barrier and are increasingly recognized as immunologically active cells. Here, we demonstrate that human and rat podocytes express enzymatically active neutrophil serine proteases (NSPs), including neutrophil elastase, proteinase 3, and cathepsin G, as well as their endogenous inhibitors, serpins. We show that the expression and activity of these proteases are regulated by pathogen- and damage-associated molecular patterns. Notably, podocytes release NSPs in extracellular vesicles and secrete mitochondrial DNA in response to inflammatory stimuli without compromising cell viability. We also identified, for the first time, the expression and redistribution of myeloperoxidase in podocytes upon stimulation. These findings reveal a previously unrecognized role of podocytes, suggesting that they may actively participate in glomerular inflammation and immune responses. The present study provides new insights into podocyte biology and opens avenues for exploring their role in kidney disease pathogenesis.