Oleic acid (OA) can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1β production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation. 1. Introduction Adult respiratory distress syndrome (ARDS) description appeared in 1967, with 12 patients with refractory cyanosis to oxygenation therapy [1]. Recently, a draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200？mm？Hg < PaO2/FIO2 ≤ 300？mm？Hg), moderate (100？mm？Hg < PaO2/FIO2 ≤ 200？mm？Hg), and severe (PaO2/FIO2 ≤ 100？mm？Hg) [2] which was nominated as Berlin definition, replacing the American-European consensus [3]. The initial lesion characterizing the exudative phase of ARDS is an increase in alveolar permeability to plasma proteins, leading to an interstitial and alveolar oedema [4, 5]. In the acute phase, cytokines and lipids are released, leading to alveolar-capillary barrier loss with hyaline membrane formation [6, 7]. In fact, ARDS is a diffuse alveolar damage secondary to an intense lung inflammatory response to an infectious, noninfectious, or extra pulmonary insult [8, 9]. ARDS can be induced by several factors such as systemic endotoxin release, pneumonia, drug overdose, acid aspiration, fat embolism, and pancreatitis [10–13] and can occur in pathological processes including sepsis, major trauma, or severe leptospirosis [8, 14, 15]. Resolution of the pulmonary oedema and lung inflammation are important determinants of ARDS outcome. Removal of alveolar fluid depends on transport of salt and water across the alveolar epithelium through apical sodium channels (ENaC) followed by extrusion to the lung interstitium via the Na-K-ATPase of alveolar epithelial cells [16–18]. Oleic acid (OA) is an inhibitor of the Na/K-ATPase activity in bovine serum [19] and is also a Na/K-ATPase inhibitor in a rabbit lung model, increasing endothelial
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