George T Noutsios1, Amanda L Willis1, Julie G Ledford2, Eugene H Chang1. 1. Department of Otolaryngology-Head & Neck Surgery, University of Arizona College of Medicine, Tucson, AZ. 2. Department of Medicine & Immunobiology, University of Arizona College of Medicine, Tucson, AZ.
Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens. Surfactant protein A (SP-A) is a member of the collectin family secreted by the airway epithelia and plays a critical role in airway innate immunity, as it can aggregate bacteria. We hypothesized that SP-A plays a role in bacterial CRS. METHODS: Air-liquid interface (ALI) cultures of nasal epithelial cells were derived from human ex-vivo healthy and CRS sinus tissues (n = 26) and challenged with PA. SP-A levels were measured with western blot and quantitative reverse transcript-polymerase chain reaction (qRT-PCR) in ALI and sinus tissues. RESULTS: We determined that SP-A: (i) mRNA and protein levels are increased significantly in CRS tissues compared with healthy sinuses; (ii) although primarily expressed in the lung, it is also synthesized and expressed in sinonasal epithelia; (ii) is expressed in the sinuses of an SP-A humanized transgenic mouse but not in SP-A knockout mice; (iv) mRNA levels are upregulated significantly during PA challenge, but protein levels are downregulated 4 hours postchallenge and upregulated at 12 hours. CONCLUSION: Our data suggest that SP-A is expressed in the sinuses and that it plays a role in the sinus innate immune responses during bacterial infections.
BACKGROUND:Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens. Surfactant protein A (SP-A) is a member of the collectin family secreted by the airway epithelia and plays a critical role in airway innate immunity, as it can aggregate bacteria. We hypothesized that SP-A plays a role in bacterial CRS. METHODS: Air-liquid interface (ALI) cultures of nasal epithelial cells were derived from human ex-vivo healthy and CRS sinus tissues (n = 26) and challenged with PA. SP-A levels were measured with western blot and quantitative reverse transcript-polymerase chain reaction (qRT-PCR) in ALI and sinus tissues. RESULTS: We determined that SP-A: (i) mRNA and protein levels are increased significantly in CRS tissues compared with healthy sinuses; (ii) although primarily expressed in the lung, it is also synthesized and expressed in sinonasal epithelia; (ii) is expressed in the sinuses of an SP-Ahumanized transgenic mouse but not in SP-A knockout mice; (iv) mRNA levels are upregulated significantly during PA challenge, but protein levels are downregulated 4 hours postchallenge and upregulated at 12 hours. CONCLUSION: Our data suggest that SP-A is expressed in the sinuses and that it plays a role in the sinus innate immune responses during bacterial infections.
Authors: Eugene H Chang; Amanda L Willis; Hilary C McCrary; George T Noutsios; Christopher H Le; Alexander G Chiu; Corrine J Mansfield; Danielle R Reed; Steven G Brooks; Nithin D Adappa; James N Palmer; Noam G Cohen; Debra A Stern; Stefano Guerra; Fernando D Martinez Journal: J Allergy Clin Immunol Date: 2016-12-03 Impact factor: 10.793
Authors: Wytske J Fokkens; Valerie J Lund; Joachim Mullol; Claus Bachert; Isam Alobid; Fuad Baroody; Noam Cohen; Anders Cervin; Richard Douglas; Philippe Gevaert; Christos Georgalas; Herman Goossens; Richard Harvey; Peter Hellings; Claire Hopkins; Nick Jones; Guy Joos; Livije Kalogjera; Bob Kern; Marek Kowalski; David Price; Herbert Riechelmann; Rodney Schlosser; Brent Senior; Mike Thomas; Elina Toskala; Richard Voegels; De Yun Wang; Peter John Wormald Journal: Rhinology Date: 2012-03 Impact factor: 3.681