Pathologic mechanical stress and endotoxin exposure increases lung endothelial microparticle shedding.

TitlePathologic mechanical stress and endotoxin exposure increases lung endothelial microparticle shedding.
Publication TypeJournal Article
Year of Publication2015
AuthorsLetsiou E, Sammani S, Zhang W, Zhou T, Quijada H, Moreno-Vinasco L, Dudek SM, Garcia JGN
JournalAm J Respir Cell Mol Biol
Volume52
Issue2
Pagination193-204
Date Published2015 Feb
ISSN Number1535-4989
KeywordsAcute Lung Injury, Animals, Cell-Derived Microparticles, Cells, Cultured, Disease Models, Animal, Endothelial Cells, Endothelium, Vascular, Endotoxins, Humans, Lipopolysaccharides, Male, Mice, Inbred C57BL, Pneumonia, Stress, Mechanical, Ventilator-Induced Lung Injury
Abstract

<p>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.</p>

DOI10.1165/rcmb.2013-0347OC
Alternate JournalAm. J. Respir. Cell Mol. Biol.
PubMed ID25029266
PubMed Central IDPMC4370243
Grant ListR01 HL094394 / HL / NHLBI NIH HHS / United States
HL94394 / HL / NHLBI NIH HHS / United States
HL058064 / HL / NHLBI NIH HHS / United States
P01 HL098050 / HL / NHLBI NIH HHS / United States
HL98050 / HL / NHLBI NIH HHS / United States
P01 HL058064 / HL / NHLBI NIH HHS / United States