Rose-Marie A Mackay1, Christopher L Grainge2, Laurie C Lau3, Clair Barber4, Howard W Clark4, Peter H Howarth4. 1. Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. Electronic address: r.a.mackay@soton.ac.uk. 2. Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia. 3. Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. 4. Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Abstract
BACKGROUND: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma. METHODS: SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size. RESULTS: SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels. CONCLUSIONS: These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.
BACKGROUND: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma. METHODS: SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size. RESULTS: SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels. CONCLUSIONS: These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways.
Authors: Ann Marie LeVine; James Elliott; Jeffrey A Whitsett; Anon Srikiatkhachorn; Erika Crouch; Nihal DeSilva; Thomas Korfhagen Journal: Am J Respir Cell Mol Biol Date: 2004-03-11 Impact factor: 6.914
Authors: Carla Winkler; Elena N Atochina-Vasserman; Olaf Holz; Michael F Beers; Veit J Erpenbeck; Norbert Krug; Stefan Roepcke; Gereon Lauer; Martin Elmlinger; Jens M Hohlfeld Journal: Respir Res Date: 2011-03-11
Authors: Michael W Sims; Ruth M Tal-Singer; Sonja Kierstein; Ali I Musani; Michael F Beers; Reynold A Panettieri; Angela Haczku Journal: Respir Res Date: 2008-01-28
Authors: Rudra Bhowmick; Tahereh Derakhshan; Yurong Liang; Jerry Ritchey; Lin Liu; Heather Gappa-Fahlenkamp Journal: Tissue Eng Part A Date: 2018-06-29 Impact factor: 3.845
Authors: Nicole P Malvin; Justin T Kern; Ta-Chiang Liu; Steven L Brody; Thaddeus S Stappenbeck Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-05-22 Impact factor: 5.464
Authors: Sylvia Ujma; William G C Horsnell; Arieh A Katz; Howard W Clark; Georgia Schäfer Journal: J Innate Immun Date: 2016-10-29 Impact factor: 7.349
Authors: Brittany N Szafran; Abdolsamad Borazjani; Caitlin N Seay; Russell L Carr; Richard Lehner; Barbara L F Kaplan; Matthew K Ross Journal: Chem Res Toxicol Date: 2021-04-26 Impact factor: 3.973
Authors: Alastair Watson; Nina Kronqvist; C Mirella Spalluto; Mark Griffiths; Karl J Staples; Tom Wilkinson; Uffe Holmskov; Grith L Sorensen; Anna Rising; Jan Johansson; Jens Madsen; Howard Clark Journal: Immunobiology Date: 2016-10-18 Impact factor: 3.144