Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia.

Juan Carlos Fernández-Martín,José G Monterde,Isaac Rosado-Sánchez,José Luis Venero,Yolanda M Pacheco,Rocío M De Pablos,Rosario Moyano,Ana María Espinosa-Oliva,Irene García-Domínguez

doi:10.3390/ijms23031170

Abstract

Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions.

Highlights

Systemic inflammation is a major pathogenic feature of different acute and chronic diseases, including sepsis [1]
The cytokine storm is triggered by leukocyte activation after binding of pathogen-associated molecular patterns (PAMPs) such as bacterial, fungal, or viral components or damage-associated molecular patterns (DAMPs) such as endogenous nucleic acid material and proteins [4]
Gram-negative bacteria widely used to model the acute inflammatory response associated with early sepsis [6]

Summary

Introduction

Systemic inflammation is a major pathogenic feature of different acute and chronic diseases, including sepsis [1]. Lipopolysaccharide (LPS)-induced endotoxemia leads to overall activation of monocytes and peripheral macrophages to cause peripheral inflammation. At appropriate LPS doses, animals exhibit physiological and biochemical features that mimic certain fulminant forms of Gram-negative bacterial infection along with important hallmarks of sepsis [2]. Sepsis/endotoxemia can lead to a systemic inflammatory response syndrome (SIRS) that induces a cytokine storm-induced syndrome, a life-threating condition [3]. The cytokine storm is triggered by leukocyte activation after binding of pathogen-associated molecular patterns (PAMPs) such as bacterial, fungal, or viral components or damage-associated molecular patterns (DAMPs) such as endogenous nucleic acid material and proteins [4]

Methods

Results

Conclusion