PT  - JOURNAL ARTICLE
AU  - Dorward, David A
AU  - Felton, Jennifer M
AU  - Robb, Calum T
AU  - Craven, Thomas
AU  - Kipari, Tiina
AU  - Walsh, Timothy S
AU  - Haslett, Christopher
AU  - Kefala, Kallirroi
AU  - Rossi, Adriano G
AU  - Lucas, Christopher D
TI  - The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome
AID  - 10.1136/thoraxjnl-2016-209229
DP  - 2017 Feb 01
TA  - Thorax
PG  - 182--185
VI  - 72
IP  - 2
4099  - http://thorax.bmj.com/content/72/2/182.short
4100  - http://thorax.bmj.com/content/72/2/182.full
SO  - Thorax2017 Feb 01; 72
AB  - Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents.