The role of purinergic P2X7 receptors on lipopolysaccharide (LPS)-induced lung injury
V. Cagido, D. Riva, D. Fonseca, W. Zin, R. Coutinho-Silva, D. Faffe (Rio de Janeiro, Brazil)
Source: Annual Congress 2007 - Acute and chronic lung injury and its repair: novel molecular insight
Disease area: Airway diseases
Abstract P2X7 receptors are ligand-gated ion channels, activated by ATP, that have been involved in inflammatory and immunological responses. Indeed, P2X7 receptor activation can modulate pro-inflammatory cytokines production by LPS-challenged macrophages. However, its relative contribution to LPS effects in vivo is unclear. This study investigates the role of P2X7 receptors on LPS-induced pulmonary lung injury in P2X7 knockout (-/- ) and wild type (WT) mice. To that end, C57Bl6 mice (n = 27) received intratracheal injection of E. coli LPS (60 μg, groups LPS-KO and LPS-WT) or saline (50 μL, groups Ctrl-KO and Ctrl-WT). After 24 h, lung mechanics and histology were analyzed. Lung static elastance (58.6 ± 14.4 cmH2 O/mL), the elastic component of viscoelasticity (12.5 ± 3.4 cmH2 O/mL), as well as total (3.0 ± 0.7 cmH2 O) and viscoelastic (1.2 ± 0.3 cmH2 O) pressures were increased in LPS-WT mice compared with WT controls (29.9 ± 5.6 cmH2 O/mL, 6.3 ± 1.8 cmH2 O/mL, 1.2 ± 0.3 cmH2 O, 1.3 ± 0.5 cmH2 O, respectively). On the other hand, LPS challenge did not induce significant changes in lung mechanics in P2X7 (-/- ) mice (36.1 ± 6.8 cmH2 O/mL, 8.2 ± 0.8 cmH2 O/mL, 1.6 ± 0.1 cmH2 O, 2.2 ± 0.2 cmH2 O, respectively) in relation to WT or P2X7 (-/- ) controls. LPS treatment also induced lower influx of polimorphonuclear cells and alveolar collapse in lung parenchyma in P2X7 (-/- ) mice (82% and 39%, respectively) than in WT mice (206% and 184%, respectively), when compared with Ctrl-KO and Ctrl-WT. In conclusion, P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammation and functional changes. Supported by: PRONEX-MCT, FAPERJ, CNPq, MCT.
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V. Cagido, D. Riva, D. Fonseca, W. Zin, R. Coutinho-Silva, D. Faffe (Rio de Janeiro, Brazil). The role of purinergic P2X7 receptors on lipopolysaccharide (LPS)-induced lung injury. Eur Respir J 2007; 30: Suppl. 51, 2693
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