title: Preactivated and Disaggregated Shape-Changed Platelets Protected Against Acute Respiratory Distress Syndrome Complicated by Sepsis Through Inflammation Suppression.
abstract: 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).
  
  
  
  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, intravenous administration]), group 3 (ARDS-LPS), and group 4 (ARDS-LPS + PreD-SCP), and sacrificed by 72 h after ARDS induction.
  
  
  
  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).
  
  
  
  PreD-SCP therapy effectively improved lung injury in ARDS complicated by sepsis.
authors.affiliation: *Department of Anesthesiology, Chang Gung Memorial Hospital, Institute of Clinical Medical Science, Chang Gung University, Taiwan †Department of Anesthesiology, National Defense Medical Center, Taiwan ‡Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan §Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan ¶Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ||Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan #Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan **Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ††Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ‡‡Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan §§Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ¶¶Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ||||Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan ##Department of Nursing, Asia University, Taichung, Taiwan.
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Chen
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Tien-Hung
authors.initials: TH
authors.lastname: Huang
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Tsung-Cheng
authors.initials: TC
authors.lastname: Yin
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Chiang
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018946:Chemokine CCL5; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase