title: Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury.
abstract: Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, excessive NETs formation and poor degradation are associated with exacerbated immune responses and tissue injury. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-mediated acute lung injury (ALI) and assessed the use of DNase I, for the treatment of ALI. Additionally, we focused on the controversial issue of whether LPS directly induces NETs release in vitro. NETs formation was detected in murine ALI tissue in vivo and was associated with increased NETs markers, citrullinated-histone H3 tissue levels and NET-DNA levels in BALF. Treatment with DNase I significantly degraded NETs and reduced citrullinated-histone H3 levels, which protected against ALI and ameliorated pulmonary oedema and total protein in BALF. In addition, DNase I significantly reduced IL-6 and TNF-α levels in plasma and BALF. In vitro, LPS-activated platelets rather than LPS alone efficiently induced NETs release. In conclusion, NETs formed during LPS-induced ALI, caused organ damage and initiated the inflammatory response. NETs degradation by DNase I promoted NET-protein clearance and protected against ALI in mice; thus, DNase I may be a new potential adjuvant for ALI therapy. Specifically, LPS induced NETs formation in an indirect manner via platelets activation.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Pinhua
authors.initials: P
authors.lastname: Pan
authors.affiliation: Department of Thoracic Medicine, Hunan Cancer Hospital, Affiliated to Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.
authors.forename: Lemeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Haosi
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh PA, 15213, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000076302:Citrullination; D003850:Deoxyribonuclease I / Q000378:metabolism; D065206:Extracellular Traps / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D006657:Histones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003850:Deoxyribonuclease I