Preactivated and Disaggregated Shape-Changed Platelets Protected Against Acute Respiratory Distress Syndrome Complicated by Sepsis Through Inflammation Suppression.

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, 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.

• Authors: Yuan-Ji Day, Kuan-Hung Chen, Yi-Ling Chen, Tien-Hung Huang, Pei-Hsun Sung, Fan-Yen Lee, Chih-Hung Chen, Han-Tan Chai, Tsung-Cheng Yin, Hsin-Ju Chiang, Sheng-Ying Chung, Hsueh-Wen Chang, Hon-Kan Yip
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 46 Issue 5 Pg. 575-586 (11 2016) ISSN: 1540-0514 [Electronic] United States
• PMID: 27058048 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL5
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Peroxidase

Topics

• Animals
• Blood Platelets (metabolism)
• Chemokine CCL5 (metabolism)
• Inflammation (immunology, metabolism, therapy)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Male
• NF-kappa B (metabolism)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Respiratory Distress Syndrome (immunology, metabolism, therapy)
• Sepsis (immunology, metabolism, therapy)
• Tumor Necrosis Factor-alpha (metabolism)