Estudo do envolvimento da adenosina na resposta inflamatória pulmonar crônica induzida por partículas de sílica em camundongos

Abstract

Silicosis is the most prevalent pneumoconiosis in Brazil and worldwide, resulting from prolonged exposure to retention of crystalline silica. It is characterized by the inflammatory and fibrogenic component, associated with a marked impairment of pulmonary function. Despite the available therapeutic arsenal, there is no effective treatment so far. Adenosine is a mediator generated from adenine nucleotides, whose action is associated with classical transmembrane metabotropic receptors and involvement in fibrotic processes has also been demonstrated. In this study, we investigated the involvement of adenosine in experimental silicosis. Mice were instilled with suspension of crystalline silica (10 mg / 50 μL / animal), (n= 6 - 8 animals per group), and were monitored at 7 (early) and 28 days (late) after silica stimulation. The following parameters were taxed: i) histology (morphology and morphometry; collagen deposition) using hematoxylin and eosin and Picrus sirius dyes; ii) pulmonary function and airway reactivity to cholinergic agonist methacholine; iii) quantification of inflammatory mediators by ELISA and iv) A2A receptor expression by western blot. It verified that the instillation of the silicas led to the increase in the expression of A2A receptors, in a time dependent manner, with more intense response being noticed in the late phase. Following, genetically depleted A2A receptor (A2A -/-) mice (Balb / c background) or Swiss-Webster mice receiving therapeutically A2A SCH 58261 antagonist administration were used, at the dose of 0.1 mg / kg (i.p.). A2A -/- as well as those composed of compound SCH 58261 did not reduce the granulomas and fibrosis (collagen fiber deposition) content without pulmonary parenchyma, in parallel to the improvement in pulmonary function evidenced by airway hyperreactivity. The reduction in the content of smooth muscle action positive cells (α-SMA) - a marker for myofibroblasts - was also evidenced. In conclusion, our results show that adenine appears to play an important role in granulomatous fibrosis found in the estimation condition with non-lung mouse silica estimates, and to suggest this mediator as a currently concerned therapeutic agent. These data are relevant to the future development process of an effective therapy to be applied in fibrotic diseases such as silicosis.