ISONIAZID - MAIN ANTI-TUBERCULOUS DRUGALTERS NEUTROPHIL EXTRACELLULAR TRAPS STRUCTURE AND TURNOVER

CASTILLO, LUIS A.; MARIN, JOSE L; SASSIAIN, MC; RODRIGUEZ RODRIGUES, N; BALBOA, LUCIANA; LANDONI, VERÓNICA I.; GARCIA, MARINA; SCHIERLOH, P.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de BioCiencias; 2017

Abstract: Drug induced lupus-like reactions are characterized bythe presence of anti-nuclear antibodies (ANA) without hypersensitivityto 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 mycobacterialperoxidase/catalase KatG (Rv1908c) to give the INH? toxic radical.Considering that Neutrophil Extracellular Traps (NETs) formationrequires enzymatically active myeloperoxidase (MPO), we asked ifthe extensive neutrophil (PMN) activation typically observed duringactive TB may lead to undesirable autoimmune reactions when itis combined with an INH-based therapy. When primary granules-containing MPO- isolated from normal human blood PMN wereincubated with INH or rifampicin -another anti-TB compound-, wefound that only the first drug was a good substrate for human MPOat therapeutic serum concentrations (Km=30±5μM; Cmax=40±15μM)giving an active product with oxidant properties (p