Pathologic mechanical stress and endotoxin exposure increases lung endothelial microparticle shedding

Eleftheria Letsiou, Saad Sammani, Wei Zhang, Tong Zhou, Hector Quijada, Liliana Moreno-Vinasco, Steven M. Dudek, Joe G.N. Garcia

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Acute lung injury (ALI) results from infectious challenges and from pathologic lung distention produced by excessive tidal volume delivered during mechanical ventilation (ventilator-induced lung injury [VILI]) and is characterized by extensive alveolar and vascular dysfunction. Identification of novel ALI therapies is hampered by the lack of effective ALI/VILI biomarkers. We explored endothelial cell (EC)-derived microparticles (EMPs) (0.1-1 μm) as potentially important markers and potential mediators of lung vascular injury in preclinical models of ALI and VILI. We characterized EMPs (annexin V and CD31 immunoreactivity) produced from human lung ECs exposed to physiologic or pathologic mechanical stress (5 or 18% cyclic stretch [CS]) or to endotoxin (LPS). EC exposure to 18% CS or to LPS resulted in increased EMP shedding compared with static cells (∼ 4-fold and ∼ 2.5-fold increases, respectively). Proteomic analysis revealed unique 18% CS-derived (n = 10) and LPS-derived EMP proteins (n = 43). VILI-challenged mice (40 ml/kg, 4 h) exhibited increased plasma and bronchoalveolar lavage CD62E (E-selectin)-positive MPs compared with control mice. Finally, mice receiving intratracheal instillation of 18% CS-derived EMPs displayed significant lung inflammation and injury. These findings indicate that ALI/VILI-producing stimuli induce significant shedding of distinct EMP populations that may serve as potential ALI biomarkers and contribute to the severity of lung injury.

Original languageEnglish (US)
Pages (from-to)193-204
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume52
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • Cyclic stretch
  • LPS
  • Microparticles
  • Proteomics
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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