IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Chemokine receptor CCR1 deficiency protects from renal damage in a murine model of hemolytic uremic syndrome.
Autor/es:
RAMOS MV; RODERO M; BENTANCOR L; COMBADIÈRE C; PALERMO MS
Lugar:
Viña del Mar, Chile
Reunión:
Congreso; 9th Lat in American Congress of Immunology (ALAI),; 2009
Institución organizadora:
Asociación Latinoamericana de Inmunología (ALAI)
Resumen:
Hemolytic Uremic Syndrome (HUS), a vascular disease characterized by nephropathy, is caused by enterohemorraghic-producing-Shiga-toxins (Stx) bacteria. The aim of the work was to determine the role of chemokine receptor CCR1 in a murine Stx2-triggered HUS model. Mice lacking CCR1 had a higher survival rate to Stx2 inoculation than control mice (%survivors:72±17.0 and 11,7±7.8,respectively,p<0.01). Creatinine increase, main marker of kidney damage,  at 3 days after Stx2 was significanlty reduced in CCR1-deficient mice compared to wild-type=(mg/dl):CCR1Ko=0.94±0.13;control=1.33±0.09,p<0.05). To analyse the involved mechanism in the lower Stx2-susceptibility of CCR1Ko, leukocyte-subpopulations implicated in endothelial damage were studied by flow cytometry. In basal condition both strains showed similar leukocyte percentages in blood or bone marrow. By day 3 after Stx2-injection, the % of mieloid cells (MC) and polymorphonuclear neutrophils (PMN) increased in blood of wild-type but not in CCR1-deficient mice (%MC:control=28,2±5,0 and CCR1Ko=18,1±4,4,p<0.01 and %PMN:control=25,0±4,9 and CCR1Ko=14,7±3,8, p<0.01). At this time MC and PMN relative numbers in bone marrow, increases similarly in both mice strains.  Our data suggest that in the mouse model of HUS, CCR1 is a key factor controlling  the circulating neutrophilia and renal injury secondary to Stx2 insult. We proposed that CCR1-deficiency by regulating the neutrophil egress from bone marrow protects renal function