Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEV1

Abstract

Background Chronic obstructive pulmonary disease (COPD) and asthma have heterogeneous inflammation with inhaled corticosteroids (ICS) as a mainstay of treatment. There is increased prevalence of non-typeable Haemophilus influenzae (NTHi) persistence in airways of patients with neutrophilic airway inflammation, potentially due to suppressed host defence after corticosteroid treatment. Antimicrobial peptides (AMPs) have antimicrobial activity against pathogens and immunomodulatory effects. We investigated whether AMPs associate with NTHi presence in COPD and asthma, and whether ICS alter this. Methods Secretory leukocyte protease inhibitor (SLPI), osteopontin, elafin and beta defensin-1 were measured in sputum supernatants from healthy donors (n=9), asthmatics (n=21) and patients with COPD (n=14). Elafin and beta defensin-1 were measured in a primary human bronchial epithelial cells (HBECs) from healthy and COPD donors infected with NTHi and pre-treated with fluticasone propionate (FP) and budesonide (BUD). Internalised NTHi was quantified by qPCR. Results Sputum SLPI was negatively correlated with FEV1 (p<0.001, r=−0.610), FEV1% predicted (p<0.001, r=−0.583) and FEV1/FVC (p=0.001, r=−0.528). Sputum beta defensin-1 was negatively associated with FEV1 (p<0.001***r=−0.594). SLPI and beta defensin-1 levels in sputum were higher in the healthy controls and COPD group compared to the asthma group (p=0.001 and p=0.014) and (p<0.001 and p=0.007, respectively). ICS use was associated with higher sputum osteopontin compared to those with no ICS use. NTHi infection of COPD HBECs produced higher levels of beta defensin-1 compared to healthy donors (mean (SD) release: 45.1pg/mL (7.3) vs 21.2pg/mL (7.3) respectively, p=0.014). Elafin release from HBECs from COPD donors did not change following NTHi infection; however, elafin from healthy donors was significantly reduced (%mean reduction: 23.7%, 95% confidence intervals (CI) of reduction: 5.3–38.4%, p<0.01). Conclusion Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function. ICS use was associated with higher sputum osteopontin compared to those with no ICS use.

Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of “asthma and chronic obstructive pulmonary disease overlap” in the elderly

“…The lung is consistently exposed to noxious stimuli, including microorganisms. Although there is a controversy regarding which comes first, infections combine with inflammatory and pathological changes in the development of asthma and COPD [ 33 ] and antimicrobial peptides from the airway epithelium have been associated with the pathologic features of both [ 34 , 35 ]. ACO cluster 2 was characterized by the enrichment of dendritic cell-associated C-type lectine-2 (Dectin-2) family and the TLR regulation by endogenous ligands pathway.…”

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

“…As for antimicrobial proteins and peptides, it has been previously shown that sputum levels of SLPI and elafin display an inverse correlation with bacterial load [228]. In a more recent study in COPD and asthmatic patients [308], an overall negative correlation between both sputum SLPI and hBD-1 and FEV 1 was found. These data highlight the potential for these AMPs to identify patients at greater risk of lung function decline.…”

Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease

“…Other effects described elsewhere include chemotaxis, angiogenesis, wound healing, antitumor, antifungal, antiviral, and less potent antimicrobial activity (279). b-defensins have been implicated in COPD pathogenesis and disease progression (297,315,(375)(376)(377)(378)(379)(380)(381). Reduced lung function has been associated with increased levels of defensins (380,(382)(383)(384).…”