Involvement of Alveolar Macrophages and Neutrophils in Acute Lung Injury After Scorpion Envenomation: New Pharmacological Targets

AbstractAndroctonus australis hector (Aah) scorpion venom is well known to induce a systemic inflammatory response associated with cell infiltration in lung and edema formation. The present study investigate (i)in vivo the evolution of lung and systemic inflammation triggered by Aah venom and (ii) analyzein vitro the signaling cascade, upstream of inflammatory cytokine expression after Aah venom-stimulated mouse alveolar macrophage (MH-S), the main resident immune cells in the lung. The inflammation induced by Aah venom was assessed in mice through inflammatory cell count, nitric oxide metabolite, and lactate dehydrogenase (LDH) activity in blood, concordantly with neutrophil sequestration in tissue and lung histology. In thein vitro study, MH-S cells are stimulated with Aah venom in the presence of signaling pathway inhibitors, NG25 an inhibitor of transforming growth factor β-activated kinase (TAK1), PD184352 MAP kinase (MKK)1/2 inhibitor, BI605906 an inhibitor of IKκ-β (inhibitor of nuclear factor kappa B), and BIRB0796 an inhibitor of p38 MAPK. Obtained results showed that leukocyte transmigration is important in some area of the lung and is closely associated wit h systemic increase of nitric oxide and LDH. Thein vitro study showed that Aah venom induce significantly an increase of the expression of TNF- α, IL-1β, and MIP-2 in MH-S cells. The pretreatment with inhibitors showed that cytokine increase involves TAK1, IKκ-β, and ERK1/2 pathways, similarly to Toll-lik...
Source: Inflammation - Category: Allergy & Immunology Source Type: research