Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia
Liang Li,
Han Chung Chong,
Say Yong Ng,
Ka Wai Kwok,
Ziqiang Teo,
Eddie Han Pin Tan,
Chee Chong Choo,
Ju Ee Seet,
Hyung Won Choi,
Martin Lindsay Buist,
Vincent Tak Kwong Chow,
Nguan Soon Tan
Affiliations
Liang Li
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Han Chung Chong
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Say Yong Ng
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Ka Wai Kwok
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Ziqiang Teo
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Eddie Han Pin Tan
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
Chee Chong Choo
Institute of Molecular and Cell Biology, A∗STAR, Singapore 138673, Singapore
Ju Ee Seet
Department of Pathology, National University Hospital, Singapore 119074, Singapore
Hyung Won Choi
Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore
Martin Lindsay Buist
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117575, Singapore
Vincent Tak Kwong Chow
Host and Pathogen Interactivity Laboratory, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Nguan Soon Tan
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore 637551, Singapore
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.
