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

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Abstract

Androctonus 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) analyze in 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 the in 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 with systemic increase of nitric oxide and LDH. The in 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-like receptor activation. These findings highlight the contribution of alveolar macrophage and their secretory products to tissue damage and made of TAK1 and ERK1/2, an interesting target in scorpion envenomation.

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Acknowledgements

H.S, F.L.D, and D.H.T gratefully acknowledge Mr. Simon Rousseau Associate Professor, Department of Medicine at McGill University, for the acceptance of H.S in Meakins-Christie Laboratories.

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  1. Faculty of Biological Sciences, Laboratory Cellular and Molecular Biology, Department Cellular and Molecular Biology, USTHB, BP32, ELAlia, Bab Ezzouar, 16111, Algiers, Algeria

    Hadjer Saidi, Fatima Laraba-Djebari & Djelila Hammoudi-Triki

  2. The Meakins-Christie Laboratories at RI-MUHC, 1001 Decarie Blvd, Montreal, Canada

    Julie Bérubé

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  1. Hadjer Saidi
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Correspondence to Fatima Laraba-Djebari.

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Saidi, H., Bérubé, J., Laraba-Djebari, F. et al. Involvement of Alveolar Macrophages and Neutrophils in Acute Lung Injury After Scorpion Envenomation: New Pharmacological Targets. Inflammation 41, 773–783 (2018). https://doi.org/10.1007/s10753-018-0731-9

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