P- and E-selectin blockade can control bacterial translocation and modulate systemic inflammatory response.
Bacterial translocation is an important phenomenon in clinical medicine and leads to an increase in patient morbidity and mortality by multiple organ failure. The selectin family plays an important role in the pathogenesis of inflammation, causing an increase in leukocyte-endothelium interactions and inducing a greater leukocyte's migration. This study considered the effect of a sulfo derivative of Sialyl-Lewis(X), GM 1998-016, that will block the P- and E-selectins interaction with a ligand, the Sialyl-Lewis(X), valuing the modulation of the systemic inflammatory response and the induced translocation. Seventy-five Wistar male rats were injected intraperitoneally with Zymosan A and treated with different doses of GM 1998-016 according to study groups. Measurements of values of qualitative and quantitative microbiology, neutrophil infiltration (myeloperoxidase), oxygen free radicals (superoxide anion, superoxide dismutase, catalase, and gluthatione peroxidase), and cytokines (tumor necrosis factor-alpha and interleukin-1beta) were taken at different times after Zymosan administration. A significant decrease of bacterial translocation, both local (MLN) and systemic (p < .05), was observed, with a decrease in the neutrophil infiltration (p < .001), the oxygen free radicals production (p < .01) and the studied cytokines (p < .01). In conclusion, GM 1998-016 showed a protective effect in an in vivo experimental model of bacterial translocation, downregulating the inflammatory response and the leukocyte-endothelium interactions.
García-Criado
Francisco J
FJ
Department of Surgery, Clinic Hospital and University of Salamanca, Salamanca, Spain. marcellobb@bol.com.br
Lozano
Francisco S
FS
Barros
Marcello B
MB
Parreño
Felipe C
FC
Fresnadillo
Maria J
MJ
García-Sánchez
José Elias
JE
Gomez-Alonso
Alberto
A
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects* / Q000276:immunology; D019040:E-Selectin / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009844:Oligosaccharides / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D019040:E-Selectin; C107334:GM 1998; D009844:Oligosaccharides; D019007:P-Selectin; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D009195:Peroxidase