Human lung cell pyroptosis following traumatic brain injury

Nadine A. Kerr, Juan Pablo De Rivero Vaccari, Oliver Umland, M. Ross Bullock, Gregory E. Conner, W. Dalton Dietrich, Robert W. Keane

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Approximately 30% of traumatic brain injured patients suffer from acute lung injury or acute respiratory distress syndrome. Our previous work revealed that extracellular vesicle (EV)-mediated inflammasome signaling plays a crucial role in the pathophysiology of traumatic brain injury (TBI)-induced lung injury. Here, serum-derived EVs from severe TBI patients were analyzed for particle size, concentration, origin, and levels of the inflammasome component, an apoptosis-associated speck-like protein containing a caspase-recruiting domain (ASC). Serum ASC levels were analyzed from EV obtained from patients that presented lung injury after TBI and compared them to EV obtained from patients that did not show any signs of lung injury. EVs were co-cultured with lung human microvascular endothelial cells (HMVEC-L) to evaluate inflammasome activation and endothelial cell pyroptosis. TBI patients had a significant increase in the number of serum-derived EVs and levels of ASC. Severe TBI patients with lung injury had a significantly higher level of ASC in serum and serum-derived EVs compared to individuals without lung injury. Only EVs isolated from head trauma patients with gunshot wounds were of neural origin. Delivery of serum-derived EVs to HMVEC-L activated the inflammasome and resulted in endothelial cell pyroptosis. Thus, serum-derived EVs and inflammasome proteins play a critical role in the pathogenesis of TBI-induced lung injury, supporting activation of an EV-mediated neural-respiratory inflammasome axis in TBI-induced lung injury.

Original languageEnglish (US)
Article number69
JournalCells
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Brain injury
  • Caspase-1
  • Extracellular vesicles
  • Inflammasome
  • Inflammation
  • Pyroptosis

ASJC Scopus subject areas

  • Medicine(all)

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