ISONIAZID - MAIN ANTI-TUBERCULOUS DRUG- ALTERS NEUTROPHIL EXTRACELLULAR TRAPS STRUCTURE AND TURNOVER

GARCÍA M; LANDONI V; CASTILLO L; RODRIGUEZ-RODRIGUES, NAHUEL; MARÍN FRANCO JL; BALBOA L; SASIAIN MC; SCHIERLOH P

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Abstract: Drug induced lupus-like reactions are characterized by the presence of anti-nuclear antibodies (ANA) without hypersensitivity to the drug itself. One of such drugs is the isoniazid (INH), an effective antimicrobial worldwide used to treat tuberculosis (TB). INH is a prodrug that needs to be activated by the mycobacterial peroxidase/catalase KatG (Rv1908c) to give the INH? toxic radical. Considering that Neutrophil Extracellular Traps (NETs) formation requires enzymatically active myeloperoxidase (MPO), we asked if the extensive neutrophil (PMN) activation typically observed during active TB may leads to undesirable autoimmune reactions when it combines with an INH-based therapy. When primary granules -containing MPO- isolated from normal human blood PMN were incubated with INH or rifampicin -another anti-TB compound-, we found that only the first drug was a good substrate for human MPO at therapeutic serum concentrations (Km=30±5µM; Cmax=40±15µM) giving an active product with oxidant properties (p