Linkage of neutrophil serine proteases and decreased surfactant protein-A (SP-A) levels in inflammatory lung disease. Issue 4 (26th March 2004)

• Record Type: Journal Article
• Authors: Rubio, F; Cooley, J; Accurso, F J; Remold-O'Donnell, E
• Is Part Of: Thorax. Volume 59:Issue 4(2004)
• Page Start: 318
• Page End: 323
• Publication Date: 2004-03-26
• Subjects: inflammation -- neutrophil serine proteases -- cathepsin G -- surfactant protein A -- cystic fibrosis; BAL, bronchoalveolar lavage -- CF, cystic fibrosis -- CRD, carbohydrate recognition domain -- DFP, diisopropyl fluorophosphate -- MeOSuc, methoxysuccinyl -- MNEI, monocyte/neutrophil elastase inhibitor -- PVDF, polyvinyldine difluoride -- SBzl, thiobenzyl ester -- SP-A, surfactant protein-A -- Suc, succinyl; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thx.2003.014902
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Background: In patients with cystic fibrosis (CF) neutrophils are recruited in excess to the airways yet pathogens are not cleared and the patients suffer from chronic infections. Recent studies have shown a deficiency in airway fluids from patients with CF and other inflammatory pulmonary conditions of surfactant protein A (SP-A), a pattern recognition molecule that facilitates uptake of microbes by macrophages and neutrophils. Methods: In vitro simulations were used to test the hypothesis that decreased SP-A levels in CF might be the result of degradation by neutrophil serine proteases. Results: Very low levels of the neutrophil granule serine proteases cathepsin G, elastase, and proteinase-3 rapidly degraded pure SP-A when tested in buffered saline. The order of potency was cathepsin G>elastase>proteinase-3. The addition of cathepsin G or elastase to normal bronchoalveolar lavage (BAL) fluid caused a dose dependent degradation of endogenous native SP-A. Cathepsin G and elastase were present in the BAL fluid from many patients with CF. Simple incubation of protease positive BAL fluid from patients with CF caused a time dependent degradation of added SP-A or, where present, endogenous SP-A. The degradation of SP-A by protease(s) in BAL fluid of patients with CF was abrogated by diisopropylfluorophosphate and monocyte/neutrophil elastase inhibitor. Conclusions: The findings strongly suggest that the neutrophil serine proteases cathepsin G and/or elastase and/or proteinase-3 contribute to degradation of SP-A and thereby diminish innate pulmonary antimicrobial defence.