Exploring the Roles of Decoy Receptor 3 in Prognosis of Acute Lung Inflammation

• Main Authors: Cheng-Yu Chen, 陳正昱
• Other Authors: Pan-Chyr Yang
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/77753259549169969487

博士 === 國立陽明大學 === 臨床醫學研究所 === 99 === The lung is vulnerable to biological or physical stress and acute lung injury is an inevitable complication at intensive inflammation. Decoy receptor 3 (DcR3) belongs to tumor necrosis factor receptor (TNFR) superfamily and is a pleiotropic immunomodulator. Polymorphonuclear leukocytes (PMNs) are the most important effector cells in acute lung injury. Recent studies revealed that DcR3 plays important roles in human diseases related to autoimmune and inflammation, including silicosis, systemic lupus erythematosus, ulcerative colitis, Crohn's disease, bacteremia, cellulitis, osteomyelitis, urosepsis, and appendicitis. The aims of this thesis are (1) to evaluate the value of DcR3 in predicting the outcomes of acute lung inflammation using multicenter cohort studies; and (2) to test the hypothesis that the inflamed lungs of DcR3 transgenic mice have abundant recruited PMNs and more neutrophil extracellular traps (NETs) formation compare to wild type mice. In one cohort of 45 healthcare-associated pneumonia (HCAP) patients, and two cohorts, 88 and 59 patients respectively, of acute respiratory distress syndrome (ARDS), patients with higher plasma DcR3 levels were associated with higher short-term and long-term mortality rates. The DcR3 levels also predict multiple-organ dysfunction syndrome and Gram-negative-bacilli infection. In a mouse model of endotoxin-induced acute lung injury, DcR3 transgenic mice had more severe lung and systemic inflammation. Ex vivo study also verified exogenous recombinant human DcR3 can promote NETs formation with dose dependent manner. Further investigations into the roles of DcR3 in the pathogenesis of ARDS may disclose better therapeutic strategies.