title: Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia.
abstract: Excessive host inflammatory responses negatively impact disease outcomes in respiratory infection. Host-pathogen interactions during the infective phase of influenza are well studied, but little is known about the host's response during the repair stage. Here, we show that influenza infection stimulated the expression of angiopoietin-like 4 (ANGPTL4) via a direct IL6-STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated lung recovery and improved lung tissue integrity. ANGPTL4-deficient mice also showed reduced lung damage and recovered faster from influenza infection when compared to their wild-type counterparts. Retrospective examination of human lung biopsy specimens from infection-induced pneumonia with tissue damage showed elevated expression of ANGPTL4 when compared to normal lung samples. These observations underscore the important role that ANGPTL4 plays in lung infection and damage and may facilitate future therapeutic strategies for the treatment of influenza pneumonia.
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117575, Singapore.
authors: Liang
authors: L
authors: Li
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore.
authors: Han Chung
authors: HC
authors: Chong
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore.
authors: Say Yong
authors: SY
authors: Ng
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore.
authors: Ka Wai
authors: KW
authors: Kwok
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore.
authors: Ziqiang
authors: Z
authors: Teo
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore.
authors: Eddie Han Pin
authors: EHP
authors: Tan
authors: Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore.
authors: Chee Chong
authors: CC
authors: Choo
authors: Department of Pathology, National University Hospital, Singapore 119074, Singapore.
authors: Ju Ee
authors: JE
authors: Seet
authors: Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.
authors: Hyung Won
authors: HW
authors: Choi
authors: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117575, Singapore.
authors: Martin Lindsay
authors: ML
authors: Buist
authors: Host and Pathogen Interactivity Laboratory, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
authors: Vincent Tak Kwong
authors: VTK
authors: Chow
authors: School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore. Electronic address: nstan@ntu.edu.sg.
authors: Nguan Soon
authors: NS
authors: Tan