INVESTIGADORES
REINA Silvia Lorena
congresos y reuniones científicas
Título:
MODULACIÓN DEL PROCESO APOPTÓTICO GLANDULAR POR ANTICUERPOS ANTI-M3 SÉRICOS DE PACIENTES CON SÍNDROME DE SJÖGREN
Autor/es:
SILVIA REINA; ENRI BORDA
Lugar:
Mar del Plata
Reunión:
Congreso; LIX Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2014
Institución organizadora:
Sociedad Argentina de Investigación Clínica (SAIC)
Resumen:
Abstract: Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets salivary and
lachrymal glands, characterized by anti-cholinergic autoantibodies directed against the M3 muscarinic
acetylcholine receptor (mAChR). The aim of this work was to evaluate if cholinergic autoantibodies
contained in IgG purified from Sjögren sera could trigger apoptosis of A253 cell line. We also
determined if caspase-3 and matrix metalloproteinase 3 (MMP-3) are involved in the induction of
A253 cell death. Our results demonstrated that anti-cholinergic autoantibodies stimulate apoptosis and
inositol phosphate (InsP) accumulation accompanied by caspase-3 activation and MMP-3 production.
All of these effects were blunted by atropine and J104794, indicating that M3 mAChRs are impacted by
the anti-cholinergic autoantibodies. The intracellular pathway leading to autoantibody-induced
biological effects involves phospholipase C (PLC), calcium/calmodulin (CaM) and extracellular calcium
as demonstrated by treatment with U-73122, W-7, verapamil, BAPTA and BAPTA-AM, all of which
blocked the effects of the anti-cholinergic autoantibodies. In conclusion, anti-cholinergic
autoantibodies in IgG purified from pSS patient's sera mediates apoptosis of the A253 cell line in an
InsP, caspase-3 and MMP-3 dependent manner.