{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:35:40Z","timestamp":1778567740247,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Medical Research Charities Group\/Health Research Board","award":["11\/RFP\/BMT\/3094"],"award-info":[{"award-number":["11\/RFP\/BMT\/3094"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["11\/RFP\/BMT\/3094"],"award-info":[{"award-number":["11\/RFP\/BMT\/3094"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US Alpha One Foundation","award":["11\/RFP\/BMT\/3094"],"award-info":[{"award-number":["11\/RFP\/BMT\/3094"]}]},{"DOI":"10.13039\/501100001592","name":"Higher Education Authority","doi-asserted-by":"publisher","award":["11\/RFP\/BMT\/3094"],"award-info":[{"award-number":["11\/RFP\/BMT\/3094"]}],"id":[{"id":"10.13039\/501100001592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Secretory leukoprotease inhibitor (SLPI) is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca<jats:sup>2+<\/jats:sup>) levels which is mediated by production of inositol 1,4,5-triphosphate (IP<jats:sub>3<\/jats:sub>) in response to G-protein-coupled receptor (GPCR) stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>10<\/mml:mn><\/mml:math>), individuals with cystic fibrosis (CF) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>5<\/mml:mn><\/mml:math>) or chronic obstructive pulmonary disease (COPD) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>5<\/mml:mn><\/mml:math>). Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP) and interleukin(IL)-8 induced neutrophil chemotaxis (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>) and decreased degranulation of matrix metalloprotease-9 (MMP-9), hCAP-18, and myeloperoxidase (MPO) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>). The mechanism of inhibition involved modulation of cytosolic IP<jats:sub>3<\/jats:sub>production and downstream Ca<jats:sup>2+<\/jats:sup>flux. The described attenuation of Ca<jats:sup>2+<\/jats:sup>flux was overcome by inclusion of exogenous IP<jats:sub>3<\/jats:sub>in electropermeabilized cells. Inhibition of IP<jats:sub>3<\/jats:sub>generation and Ca<jats:sup>2+<\/jats:sup>flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.<\/jats:p>","DOI":"10.1155\/2013\/560141","type":"journal-article","created":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T21:01:20Z","timestamp":1377810080000},"page":"1-18","source":"Crossref","is-referenced-by-count":13,"title":["Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease"],"prefix":"10.1155","volume":"2013","author":[{"given":"Emer P.","family":"Reeves","sequence":"first","affiliation":[{"name":"Respiratory Research Division, Department of Medicine, 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