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, Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia, Cell Reports, Volume 10, Issue 5, 10 February 2015, Pages 654-663, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2015.01.011.
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.