INVESTIGADORES
FRANK fernanda Maria
congresos y reuniones científicas
Título:
Cruzipain is able to revert the hepatotoxic effect elicited by oligodeoxinucleotides CpG.
Autor/es:
FRANK FM; SARTORI MJ; DELETTIERES D; CAZORLA SI; ARNAIZ M; MALCHIODI EL
Lugar:
Córdoba
Reunión:
Congreso; VIIº Congreso Latinoamericano de Inmunología; 2005
Resumen:
CpG-containing oligonucleotides (ODN-CpG) are potent stimulators of innate immunity and are being tested as adjuvants.  We have recently demonstrated the capacity of  ODN-CpG plus cruzipain (Cz) to immunoprotect mice against ChagaLs disease (Vaccine 22:77, 2003). ODN-CpG can trigger macrophages (Mo) to release large amounts of TNF-ƒ¿. Systemic accumulation of TNF-ƒ¿ in sensitised mice lead them to lethal toxic shock, resulting in fulminant apoptosis of liver cells. (Eur J Immonol 27:1671, 1997).  We decided to examine the capacity of Cz in modulate the toxic effect of ODN-CpG, since Cz is able to modulate the immune response by increasing IL-10 and TGF-ƒÀ secretion by Mo (J Leukoc Biol 72:727, 2002) In vitro, J774 Mo stimulated for 20h with ODN-CpG (1ƒÊg/ml) elicited 3 folds more TNF-ƒ¿ than cells cultured with ODN-CpG plus 10ƒÊg/ml of Cz (903.3 vs 313.6 pg/ml). Control cells cultered with Cz alone presented same levels of  TNF-ƒ¿ than control without stimulation. In vivo, C3H mice were immunised twice with GI- PBS, GII- CpG (100ƒÊg) and GIII-CpG + Cz (10 ƒÊg) and 15 days after last immunisation, livers were removed for histological studies. Hoesht, H/E and TUNNEL were used to measure hepatocyte apoptosis. No significative difference was observed between GI and III (0}0.7 and 0.2}1.2). GII presented significantly more apoptotic bodys (2.6}0.7). By H/E microscopical observation, no pathology was observed in GI and focal Kupper cell hyperplasia  were observed in hepatic tissue of GIII. Micro and macroabscess were observed in GII livers, accompanied with perivascular unicellular necrosis. Small chronic inflammatory infiltrates around central vein were also observed. We conclude that Cz is able to prevent the toxic effects of ODN-CpG, making the combination Cz+ODN-CpG safe and usefull for vaccination.