IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Decreased response of neutrophils from endotoxin tolerant mice towards lipopolysaccharide
Autor/es:
M. F. LOPEZ; V. I. LANDONI; B. REARTE; P. CHIARELLA; E. LABORDE; M. V. RAMOS; L. V. BENTANCOR; R. J. FERNANDEZ-BRANDO; M. A. ISTURIZ; M. S. PALERMO; G. C. FERNANDEZ
Lugar:
Rio de Janeiro, Brasil
Reunión:
Congreso; 13th International Congress of Immunology; 2007
Institución organizadora:
International Union of Immunological Societies
Resumen:
The immune response in sepsis shows a bimodal pattern consisting of an early inflammatory response frequently followed by a state of immunesuppression, which has been associated with a poor outcome. Neutrophils (PMN) are central in the defense against pathogens. We investigated PMN characteristics in a murine model that resembles sepsis-associated immunesuppression (tolerance to endotoxin or lipopolysaccharide, LPS). Mice were made tolerant by daily injections with low doses of LPS (5mg/mouse, Tol) or saline (Control). A final high dose of LPS (100 mg/mouse, challenge) both in control (Control+LPS) and tolerant mice (Tol+LPS) was then administered. Peripheral PMN counts, the expression of activation markers, and reactive oxygen species (ROS) generation were determined. Once tolerance was established, tolerant and control animals showed similar peripheral PMN counts. However, the challenge caused neutropenia 2h post-injection in control, but not tolerant mice (PMN/mm3: Control+LPS=435±101,Tol+LPS=1069±208#, #p<0.05 vs. Control+LPS). Tolerant animals showed an expansion of a subpopulation of CD11blowCD62Lhigh PMN, that decreased, but remained high, after challenge (%CD11blowCD62Lhigh: Control=10.8±2.2,Tol=53.5±8.6*, Control+LPS=4.0±1.8,Tol+LPS=29.2±11.8*#, *p<0.05 vs. Control,#p<0.05 vs. Control+LPS). CD11b expression in CD11blowCD62Lhigh PMN was similar between groups, but tolerant CD11bhighCD62Llow PMN showed a decreased CD11b expression before and after challenge (mean fluorescence intensity: Control=150±9,Tol=116±6*, Control+LPS=332±114*†,Tol+LPS=146±16#†, *p<0.05 vs. Control,†p<0.05 vs. Tol,#p<0.05 vs. Control+LPS). ROS generation in tolerant PMN was increased, but in contrast to control PMN, did not change after challenge (%ROS-producing cells: Control=8.7±2.0,Tol=32.3±8.8*, Control+LPS=24.1±3.0*,Tol+LPS=32.6±13.3*, *p<0.05 vs. Control). Tolerant PMN showed phenotypical and functional differences and their response towards LPS challenge was decreased, explaining the increased susceptibility to infections in sepsis-associated immunesuppression.