Monosodium urate crystals exacerbate acute lung injury induced by lipopolysaccharide.

Uric acid (UA) is a damage-associated molecular pattern (DAMP) released from injured or infected cells. Beyond maximal solubility, UA precipitates and forms monosodium urate (MSU) crystals which can activate the innate immune system. UA levels are increased in several respiratory diseases including ARDS, pulmonary hypertension or COPD. The aim of this study was to analyse whether MSU crystals are able to induce pulmonary inflammation on their own or might exacerbate the lung injury induced by lipopolysaccharide (LPS).Rats received an intratracheal instillation of saline solution (Ctrl), LPS (300 μg/Kg), MSU (10mg/Kg) or a combination of both agonists. Four hours after instillation, rats were anaesthetised and pulmonary arterial pressure (PAP) was registered in open-chest rats. Myeloperoxidase (MPO) activity and levels of IL-6 and IL-1β (determined by ELISA) were quantified in lung homogenates.Intratracheal administration of LPS increased MPO activity and IL-1β levels in lung homogenates but had no significant effects on PAP or IL-6 production. Instillation of MSU had no significant effects on pulmonary haemodynamics or inflammatory biomarkers. By contrast, simultaneous administration of MSU crystals and LPS had an additive effect on lung MPO activity, IL-6 production and induced acute pulmonary hypertension.In summary, our data suggest that MSU crystals exacerbates the development of pulmonary hypertension and lung inflammation induced by endotoxin. These finding...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of Lung Injury and Repair Source Type: research