P- and E-Selectin Blockade Can Control Bacterial Translocation and Modulate Systemic Inflammatory Response

Abstract

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.

Endothelial Cell Aging and Apoptosis in Prevention and Disease: E-Selectin Expression and Modulation As A Model

“…The most common modification associated with endothelium functional impairment is alteration of leukocyte and lymphocyte adhesion proteins, whose expression is regulated by inflammatory cytokines. E-selectin is one of the genes activated by p65 that appears to play a pivotal role in several vascular and metastatic diseases [14][15][16]. While this movement of leucocytes is important in mounting the immune and inflammatory responses and in the homing of leucocytes to lymphoid organs, it also appears to play an important role in the development of atherosclerosis, chronic inflammatory disease and metastasis dissemination [8][9][10][11][12].…”

Adhesive capability of Lactobacillus plantarum 299v is important for preventing bacterial translocation in endotoxemic rats

“…In a septic state, where the mucosal barrier and immune response are compromised, translocation occurs to such an extent that viable bacteria are able to reach extraintestinal sites, as shown in the positive control group in the present study and by others (20, 21). BT to MLN in animal studies varies between 40–100% (15, 22). In this study, BT to MLN was 25% in the positive control group, which indicates the great variation in the rate of translocation between rat species and even between rats of the same species.…”