IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Expression of Fractalkine Receptor (CX3CR1) in Monocytes and Natural iller cells from Hemolytic Uremic Syndrome Patients
Autor/es:
MARÍA VICTORIA RAMOS; GABRIELA FERNÁNDEZ; PABLO SHIERLOH; CRISTIAN ELÍAS COSTA; GRACIELA VALLEJO; RAMÓN EXENI; MARTA ALDUNCIN; FRANCOIS PROULX; MARIA DEL CARMEN SASIAIN; MARINA PALERMO
Lugar:
Melbourne, Australia
Reunión:
Simposio; VTEC 2006. 6th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections; 2006
Resumen:
Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These are related to endothelial and epithelial cell damages induced by Shiga toxin (Stx), but inflammatory processes may contribute to the pathogenesis of HUS. Fractalkine (FKN), a CX3C transmembrane chemokine expressed mainly on activated or injured endothelial cells, is involved in the selective migration and adhesion to tissues of specific subsets of leukocytes which express its receptor (CX3CR1). Subsets of monocytes (Mo) and Natural Killer (NK) cells express CX3CR1. Then, we investigated whether the expression of CX3CR1 is modulated in distinct whole blood populations from HUS patients and healthy children (HC) by flow cytometry.  We found in HUS patients, a selective depletion of circulating leukocytes expressing the CX3CR1 (HC= 31.8+2.4 %; HUS= 15.7+2.5 %, n=11, p<0.001). To further study Mo population, we analyzed the expression of CX3CR1 in combination with CD14, CD16 and CD62L. Mo expressing CX3CR1 was significantly decreased in HUS (% CX3CR1+ Mo in HC= 84.6± 2.7%, n=22; HUS= 55.5±4.0 %, n=33; p< 0.0001). Other alterations in Mo subsets include increase in CD16 expression and lost of CD62L. We analyzed the NK population by staining CD3, CD56 and CX3CR1 antigens.  We found a decreased percentage of CD56dim/CX3CR1+ NK cells in HUS patients (HC=7.3±1.3, n=16; HUS=2.4±0.6, n=10, p<0.005), leading to the alteration of the normal CD56dim:CD56bright ratio from 10.0 to 4.5.  We also found a negative correlation between the % CX3CR1+ circulating leukocytes and the severity of renal failure(r= -0.62; n=25, p=0.001). A common feature of decreased CX3CR1+ leukocytes (Mo and NK) is observed in HUS patients. Possible explanations include downmodulation or lost of CX3CR1, and/or adhesion of CX3CR1+ cells to the endothelium upon its activation during HUS. Correlation studies suggest that these abnormalities are related to the pathogenesis of HUS.