Increased MUC1 plus a larger quantity and complex size for MUC5AC in the peripheral airway lumen of long-term tobacco smokers

Padra, Médea; Andersson, Anders; Levänen, Bettina; Premaratne, Pushpa; Ásgeirsdóttir, Helga; Tengvall, Sara; Christenson, Karin; Stockfelt, Marit; Bozinovski, Steven; Yoshihara, Shigemi; Lantz, Ann-Sofie; Palmberg, Lena; Dahlén, Barbro; Larsson, K; Qvarfordt, Ingemar; Lindén, Sara K.; Lindén, Anders

doi:10.1042/cs20191085

Cited by 9 publications

(21 citation statements)

References 43 publications

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“…A detailed description of the study protocol has been published elsewhere [17]. At the individual level, certain data have been utilized in the referred publication but within the scope of another scientific aim.…”

Section: Study Population and Designmentioning

confidence: 99%

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Stockfelt¹,

Christenson²,

Andersson³

et al. 2020

J Innate Immun

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There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as neutrophils extravasate, and whether surface density of CD11b and CD62L differs between long-term tobacco smokers (LTS) with and without COPD compared with healthy never-smokers (HNS). Unstimulated blood neutrophils from LTS with (n = 5) and without (n = 9) COPD displayed lower surface density of CD62L compared with HNS (n = 8). In addition, surface density of CD11b was higher in bronchoalveolar lavage (BAL) neutrophils from LTS without COPD compared with those with COPD and HNS. Moreover, in BAL neutrophils from all study groups, CD62L was lower compared with matched blood neutrophils. In addition, BAL neutrophils responded with a further decrease in CD62L to ex vivo TNF stimulation. Thus, neutrophils in the airway lumen display a higher state of priming than systemic neutrophils and bear the potential to be further primed by local cytokines even with no smoking or the presence of COPD, findings that may represent a universal host defense mechanism against local bacteria. Moreover, systemic neutrophils are primed in LTS regardless of COPD. Further studies in larger materials are warranted to determine whether the priming of neutrophils is protective against COPD or merely preceding it.

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Section: Study Population and Designmentioning

confidence: 99%

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Stockfelt¹,

Christenson²,

Andersson³

et al. 2020

J Innate Immun

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“…Some data from this study population have previously been published, although in a different scientific context. 28 , 39 , 40 …”

Section: Methodsmentioning

confidence: 99%

“…A more detailed protocol for the sample collection, process and analysis has been described elsewhere. 39 …”

Section: Methodsmentioning

confidence: 99%

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Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD

Pournaras¹,

Andersson²,

Kovach³

et al. 2022

COPD

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Purpose Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are common comorbidities in chronic obstructive pulmonary disease (COPD), but the underlying pathogenic mechanisms are poorly understood. Given that these morbidities all display increased neutrophil mobilization, the current study aimed to address whether glucose homeostasis relates to signs of neutrophil mobilization in COPD. Methods The study population included healthy non-smokers (HNS) and long-term smokers without (LTS) and with COPD (LTS+COPD). No subject had T2DM or MetS. Serum cotinine was quantified to evaluate current smoking. Capillary blood glucose was measured after overnight fasting and during an oral glucose tolerance test (OGTT). Neutrophils were quantified in blood and bronchoalveolar lavage samples (BAL). The neutrophil-related cytokines IL-36α, -β and -γ were quantified (ELISA) along with IL-6, IL-8, INF-γ and CXCL10 (U-Plex ® ) in plasma and cell-free BAL fluid (BALF). In addition, we quantified neutrophil elastase (ELISA) and net proteinase activity (substrate assay) in BALF. Results The LTS+COPD group had lower fasting glucose, greater change in glucose during OGTT and higher neutrophil concentrations in BAL and blood compared with HNS. Fasting glucose correlated in a positive manner with blood neutrophil concentration, forced expiratory volume in 1 second/forced vital capacity ratio (FEV 1 /FVC) and FEV 1 (% of predicted) in LTS+COPD. In this group, the concentration of IL-36α in BALF correlated in a negative manner with fasting glucose, blood neutrophil concentration and FEV 1 , while the CXCL10 concentration in BALF correlated in a negative manner with glucose at the end of OGTT (120 min). We observed no corresponding correlations for neutrophil elastase, net proteinase or gelatinase activity. Conclusion In smokers with COPD, altered glucose homeostasis is associated with local and systemic signs of increased neutrophil mobilization, but not with local proteinases. This suggests that other specific aspects of neutrophil mobilization constitute pathogenic factors that affect glucose homeostasis in COPD.

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“…MUC5AC is the prime mucin of airway epithelia, which often abnormally expresses and is associated with airflow obstruction and airway hyperresponsiveness in patients with COPD [96,97]. Nie et al comprehensively investigated the expectorant mechanisms of naringenin in epidermal growth factor (EGF)-induced A549 cells [98].…”

Section: Expectorantmentioning

confidence: 99%

Evaluation of Naringenin as a Promising Treatment Option for COPD Based on Literature Review and Network Pharmacology

Chen

et al. 2020

Biomolecules

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Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incompletely reversible airflow limitation and seriously threatens the health of humans due to its high morbidity and mortality. Naringenin, as a natural flavanone, has shown various potential pharmacological activities against multiple pathological stages of COPD, but available studies are scattered and unsystematic. Thus, we combined literature review with network pharmacology analysis to evaluate the potential therapeutic effects of naringenin on COPD and predict its underlying mechanisms, expecting to provide a promising tactic for clinical treatment of COPD.

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Increased MUC1 plus a larger quantity and complex size for MUC5AC in the peripheral airway lumen of long-term tobacco smokers

Cited by 9 publications

References 43 publications

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD

Evaluation of Naringenin as a Promising Treatment Option for COPD Based on Literature Review and Network Pharmacology

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