caa a22 4500 445885203 CHVBK 20180317145557.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00011-011-0313-x doi (NATIONALLICENCE)springer-10.1007/s00011-011-0313-x Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice [Elektronische Daten] [Xiao Su, Mark Looney, Hang Su, Jae Lee, Yuanlin Song, Michael Matthay] Objective and design: Cystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury. Materials and methods: CFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response. Results: Pharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution. Conclusions: Lack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury. The Author(s), 2011 Cystic fibrosis transmembrane conductance regulator nationallicence Neutrophils nationallicence Cytokine nationallicence Lipopolysaccharide nationallicence Bone marrow transplantation nationallicence Su Xiao Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut Looney Mark Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut Su Hang Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut Lee Jae Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut Song Yuanlin Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA aut Matthay Michael Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 619-632 1023-3830 60:7<619 2011 60 11 https://doi.org/10.1007/s00011-011-0313-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0313-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Su Xiao Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Looney Mark Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Su Hang Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Lee Jae Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Song Yuanlin Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Matthay Michael Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, 94143-0130, San Francisco, CA, USA aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 619-632 1023-3830 60:7<619 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer