Abdullah A Tarique1, Peter D Sly2, Patrick G Holt3, Anthony Bosco4, Robert S Ware1, Jayden Logan1, Scott C Bell5, Claire E Wainwright6, Emmanuelle Fantino1. 1. Child Health Research Centre, The University of Queensland, Brisbane, Australia. 2. Child Health Research Centre, The University of Queensland, Brisbane, Australia; Department of Respiratory and Sleep Medicine, Children's Health Queensland, Brisbane, Australia. Electronic address: p.sly@uq.edu.au. 3. Child Health Research Centre, The University of Queensland, Brisbane, Australia; Telethon Kids Institute, University of Western Australia, Perth, Australia. 4. Telethon Kids Institute, University of Western Australia, Perth, Australia. 5. QIMR Berghofer Medical Research Institute, Brisbane, Australia; Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia. 6. Child Health Research Centre, The University of Queensland, Brisbane, Australia; Department of Respiratory and Sleep Medicine, Children's Health Queensland, Brisbane, Australia.
Abstract
BACKGROUND: The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. METHODS: Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. RESULTS: In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CONCLUSIONS: CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease.
BACKGROUND: The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. METHODS: Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. RESULTS: In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CONCLUSIONS:CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease.
Authors: Thomas Scambler; Jonathan Holbrook; Sinisa Savic; Michael F McDermott; Daniel Peckham Journal: Immunology Date: 2018-04-19 Impact factor: 7.397
Authors: H F Hazlett; T H Hampton; D S Aridgides; D A Armstrong; J A Dessaint; D L Mellinger; A B Nymon; A Ashare Journal: Sci Rep Date: 2020-07-02 Impact factor: 4.379
Authors: Amber R Philp; Texia T Riquelme; Pamela Millar-Büchner; Rodrigo González; Francisco V Sepúlveda; L Pablo Cid; Carlos A Flores Journal: Sci Rep Date: 2018-06-18 Impact factor: 4.379
Authors: Youdinghuan Chen; David A Armstrong; Lucas A Salas; Haley F Hazlett; Amanda B Nymon; John A Dessaint; Daniel S Aridgides; Diane L Mellinger; Xiaoying Liu; Brock C Christensen; Alix Ashare Journal: Clin Epigenetics Date: 2018-12-10 Impact factor: 6.551
Authors: Vincent D Giacalone; Brian S Dobosh; Amit Gaggar; Rabindra Tirouvanziam; Camilla Margaroli Journal: Int J Mol Sci Date: 2020-05-08 Impact factor: 5.923
Authors: Shuzhong Zhang; Chandra L Shrestha; Benjamin L Wisniewski; Hanh Pham; Xucheng Hou; Wenqing Li; Yizhou Dong; Benjamin T Kopp Journal: Front Immunol Date: 2020-08-18 Impact factor: 7.561