Human Lung Cell Pyroptosis Following Traumatic Brain Injury

Nadine Kerr,Oliver Umland,Robert Keane,W Dietrich,Gregory Conner,M Bullock,Juan De Rivero Vaccari

doi:10.3390/cells8010069

Nadine Kerr, Oliver Umland + Show 5 more

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https://doi.org/10.3390/cells8010069

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Journal: Cells	Publication Date: Jan 18, 2019
Citations: 45	License type: CC BY 4.0

Affiliation: University of Miami, Neurological Surgery

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.

Highlights

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common extracranial complications of traumatic brain injury (TBI) [1]
TBI patients is of respiratory major clinical importance critical care medicine
We have recently shown that extracellular vesicle (EV)-mediated causes of non-neurological death in TBI

Summary

Introduction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common extracranial complications of traumatic brain injury (TBI) [1]. Both of these conditions have been reported in up to 30% of head trauma subjects with a mortality rate close to 40% [2]. One of the hallmarks of ALI is pulmonary edema, which is due to increased endothelial permeability [3]. Pulmonary endothelial cells regulate responses from the innate immune system by releasing inflammatory molecules and mediators that aid in host defense mechanisms [4]

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