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Inflammation
Published in: Inflammation 3/2018

01-06-2018 | ORIGINAL ARTICLE

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

Authors: Hadjer Saidi, Julie Bérubé, Fatima Laraba-Djebari, Djelila Hammoudi-Triki

Published in: Inflammation | Issue 3/2018

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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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Metadata
Title
Involvement of Alveolar Macrophages and Neutrophils in Acute Lung Injury After Scorpion Envenomation: New Pharmacological Targets
Authors
Hadjer Saidi
Julie Bérubé
Fatima Laraba-Djebari
Djelila Hammoudi-Triki
Publication date
01-06-2018
Publisher
Springer US
Published in
Inflammation / Issue 3/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-0731-9

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