Helge Haarmann

The Moraxella catarrhalis-induced pro-inflammatory immune response is enhanced by the activation of the epidermal growth factor receptor in human pulmonary epithelial cells.

BACKGROUND Chronic lower airway inflammation is considered to be a major cause of pathogenesis and disease progression in chronic obstructive pulmonary disease (COPD). Moraxella catarrhalis is a COPD-associated pathogen causing exacerbations and bacterial colonization in the lower airways of patients, which may contribute to chronic inflammation. Increasing evidence suggests that the epidermal growth factor receptor (EGFR) modulates inflammatory processes in the human airways. The goal of this study was to investigate the role of EGFR in the M. catarrhalis-induced pro-inflammatory immune response in airway epithelial cells. METHODS The effects of inhibition and gene silencing of EGFR on M. catarrhalis-dependent pro-inflammatory cytokine expression in human primary bronchial epithelial cells (NHBEs), as well as the pulmonary epithelial cell lines BEAS-2B and A549 were analyzed. We also assessed the involvement of EGFR-dependent ERK and NF-κB signaling pathways. RESULTS The M. catarrhalis-induced pro-inflammatory immune response depends, at least in part, on the phosphorylation and activation of the EGF receptor. Interaction of M. catarrhalis with EGFR increases the secretion of pro-inflammatory cytokines, which is mediated via ERK and NF-κB activation. CONCLUSION The interaction between M. catarrhalis and EGFR increases airway inflammation caused by this pathogen. Our data suggest that the inhibition of EGFR signaling in COPD could be an interesting target for reducing M. catarrhalis-induced airway inflammation.

Sympathetic Activation is Associated with Exercise Limitation in COPD.

ABSTRACT Exercise intolerance, skeletal muscle dysfunction, and reduced daily activity are central in COPD patients and closely related to quality of life and prognosis. Studies assessing muscle exercise have revealed an increase in sympathetic outflow as a link to muscle hypoperfusion and exercise limitation. Our primary hypothesis was that muscle sympathetic nerve activity (MSNA) correlates with exercise limitation in COPD. MSNA was evaluated at rest and during dynamic or static handgrip exercise. Additionally, we assessed heart rate, blood pressure, CO2 tension, oxygen saturation (SpO2), and breathing frequency. Ergospirometry was performed to evaluate exercise capacity. We assessed MSNA of 14 COPD patients and 8 controls. In patients, MSNA was negatively correlated with peak oxygen uptake (VO2% pred) (r = −0.597; p = 0.040). During dynamic or static handgrip exercise, patients exhibited a significant increase in MSNA, which was not observed in the control group. The increase in MSNA during dynamic handgrip was highly negatively correlated with peak exercise capacity in Watts (w) and peak oxygen uptake (VO2/kg) (r = −0.853; p = 0.002 and r = −0.881; p = 0.002, respectively). Our study reveals an association between increased MSNA and limited exercise capacity in patients with COPD. Furthermore, we found an increased sympathetic response to moderate physical exercise (handgrip), which may contribute to exercise intolerance in COPD.

Moraxella catarrhalis decreases antiviral innate immune responses by down-regulation of TLR3 via inhibition of p53 in human bronchial epithelial cells

Chronic obstructive pulmonary disease (COPD) is complicated by infectious exacerbations with acute worsening of respiratory symptoms. Coinfections of bacterial and viral pathogens are associated with more severe exacerbations. Moraxella catarrhalis is one of the most frequent lower respiratory tract pathogens detected in COPD. We therefore studied the impact of M. catarrhalis on the antiviral innate immune response that is mediated via TLR3 and p53. Molecular interactions between M. catarrhalis and normal human bronchial epithelial (NHBE) cells as well as Beas‐2B cells were studied using flow cytometry, quantitative PCR analysis, chromatin immunoprecipitation, RNA interference, and ELISA. M. catarrhalis induces a significant down‐regulation of TLR3 in human bronchial epithelial cells. In M. catarrhalis‐infected cells, expression of p53 was decreased. We detected a reduced binding of p53 to the tlr3 promoter, resulting in reduced TLR3 gene transcription. M. catarrhalis diminished the TLR3‐dependent secretion of IFN‐β, IFN‐λ, and chemokine (C‐X‐C motif) ligand 8. In addition in M. catarrhalis infected cells, expression of rhinovirus type 1A RNA was increased compared with uninfected cells. M. catarrhalis reduces antiviral defense functions of bronchial epithelial cells, which may increase susceptibility to viral infections.—Heinrich, A., Haarmann, H., Zahradnik, S., Frenzel, K., Schreiber, F., Klassert, T. E., Heyl, K. A., Endres, A.‐S., Schmidtke, M., Hofmann, J., Slevogt, H. Moraxella catarrhalis decreases antiviral innate immune responses by down‐regulation of TLR3 via inhibition of p53 in human bronchial epithelial cells. FASEB J. 30, 2426–2434 (2016). www.fasebj.org

EBUS-TBNA in a case of mediastinal lymphangioma.

Mediastinal lymphangioma is a rare benign tumor that can be a cause of dyspnea. In our case, endobronchial ultrasound-transbronchial needle aspiration in addition to computed tomography imaging was a useful diagnostic tool in narrowing down the differential diagnosis of this mediastinal mass and to find a suitable therapeutic intervention.