Preactivated and Disaggregated Shape-Changed Platelets Protected Against Acute Respiratory Distress Syndrome Complicated by Sepsis Through Inflammation Suppression. Issue 5 (November 2016)

• Record Type: Journal Article
• Authors: Day, Yuan-Ji; Chen, Kuan-Hung; Chen, Yi-Ling; Huang, Tien-Hung; Sung, Pei-Hsun; Lee, Fan-Yen; Chen, Chih-Hung; Chai, Han-Tan; Yin, Tsung-Cheng; Chiang, Hsin-Ju; Chung, Sheng-Ying; Chang, Hsueh-Wen; Yip, Hon-Kan
• Is Part Of: Shock. Volume 46:Issue 5(2016:Nov.)
• Page Start: 575
• Page End: 586
• Publication Date: 2016-11
• Subjects: Acute lung injury -- anti-inflammation -- apoptosis -- ischemia-reperfusion -- oxidative stress -- proinflammatory cytokines; ACD -- acid citrate dextrose -- ALI -- acute lung injury -- ARDS -- acute respiratory distress syndrome -- BAL -- bronchoalveolar lavage -- BMP -- bone morphogenetic protein -- c-PARP -- cleaved poly ADP ribose polymerase -- DNPH -- Dinitrophenylhydrazine -- IF -- immunofluorescent -- IHC -- immunohistochemical -- IL -- interleukin -- iNOS -- inducible nitric oxide synthase -- LPS -- lipopolysaccharide -- MMP -- matrix metallopeptidase -- MPO -- myeloperoxidase -- NC -- normal control -- NF -- nuclear factor -- PBMNCs -- peripheral blood mononuclear cells -- PGI2 -- prostaglandin I2 -- PreD-SCP -- preactivated and disaggregated shape-changed platelet -- ROS -- reactive oxygen species -- SaO2 -- arterial oxygen saturation -- SD -- Sprague-Dawley -- TGF -- transforming growth factor -- TNF -- tumor necrosis factor -- Tregs -- regulatory T cells -- VCAM -- vascular cell adhesion protein; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000617
• Languages: English
• ISSNs: 1073-2322

Abstract

ABSTRACT: Background: This study tested the hypothesis that preactivated and disaggregated shape-changed platelet (PreD-SCP) therapy attenuates lung injury from acute respiratory distress syndrome (ARDS) induced by 100% oxygen inhalation and complicated by sepsis through peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS). Methods: Adult male Sprague-Dawley rats, weighing 325 to 350 g, were randomized into group 1 (normal controls [NC]), group 2 (NC + PreD-SCP [3.0 × 10 8, intravenous administration]), group 3 (ARDS-LPS), and group 4 (ARDS-LPS + PreD-SCP), and sacrificed by 72 h after ARDS induction. Results: The lung injury score was significantly higher in group 3 than that in other groups, and significantly higher in group 4 than that in groups 1 and 2, whereas the numbers of alveolar sacs and oxygen saturation (%) showed a reversed pattern compared with that of lung injury score among the four groups (all P < 0.0001) without significant difference between groups 1 and 2. The expressions of proinflammatory cells (CD11+, CD14+, CD68+) and proteins (tumor necrosis factor [TNF]-α, nuclear factor [NF]-κB, interleukin [IL]-1ββ, matrix metalloproteinase [MMP]-9, inducible nitric oxide synthase, intercellular adhesion molecule-1) exhibited a pattern identical to the lung injury score. Circulating levels of white blood cell, IL-6, TNF-α, myeloperoxidase and CCL5, and pulmonary protein expressions of oxidative stress (NOX-1/NOX-2, oxidized protein), apoptotic (Bax, cleaved caspase 3/poly (ADP-ribose) polymerase), fibrotic (Smad3, transforming growth factor [TGF]-β), and DNA damage (γ-H2AX) biomarkers showed an identical pattern, whereas protein expressions of antifibrotic (Smad1/5, bone morphogenetic protein [BMP]-2) and anti-inflammatory (Bcl-2) biomarkers demonstrated an opposite pattern compared with the proinflammatory indices among the four groups (all P < 0.001). Conclusions: PreD-SCP therapy effectively improved lung injury in ARDS complicated by sepsis.