Therapeutic administration of an anti-podoplanin antibody (α-PDPN) is beneficial during a mouse model of acute respiratory distress syndrome. Therapeutic.

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Large-Animal Models of Acute Respiratory Distress Syndrome
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Therapeutic administration of an anti-podoplanin antibody (α-PDPN) is beneficial during a mouse model of acute respiratory distress syndrome. Therapeutic administration of an anti-podoplanin antibody (α-PDPN) is beneficial during a mouse model of acute respiratory distress syndrome. (A) Sao2 (P<0.001) and activity (P=0.043) were measured by MouseOx Plus, as well as cumulative weight change of wildtype mice (P=0.007) given intravenous phosphate-buffered saline (PBS) or α-PDPN 6 hours after intratracheal (IT) instillation of lipopolysaccharide (LPS). Mice were monitored for 9 days after IT-LPS (intravenous PBS n=8, intravenous α-PDPN n=7; mean±SEM). Two-way repeated-measures analysis of variance was performed with Sidak’s multiple comparisons test. (B) H&E staining of lungs from wildtype mice given α-PDPN 6 hours after IT instillation of LPS compared with controls (n=4). Bar, 100 µm. (C) Bronchoalveolar lavage (BAL) neutrophilia, total BAL protein and lung wet:dry weight ratio were measured 48 hours after IT-LPS in wildtype mice given intravenous PBS or α-PDPN 6 hours after IT instillation of LPS (BAL neutrophilia and protein n=10; wet:dry ratio n=6). Student’s t-tests were performed. (D) Expression of cytokines/chemokines in BAL were measured 48 hours after IT-LPS in wildtype mice given intravenous PBS or α-PDPN 6 hours after IT instillation of LPS (n=6). Student’s t-tests were performed. *P<0.05; **P<0.01. IL-6, interleukin-6; TNFα, tumour necrosis factor alpha. Sian Lax et al. BMJ Open Resp Res 2017;4:e000257 ©2017 by British Thoracic Society