Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

John-Schuster, Gerrit; Hager, Katrin; Conlon, Thomas M.; Irmler, Martin; Beckers, Johannes; Eickelberg, Oliver; Yildirim, Ali Önder

doi:10.1152/ajplung.00092.2014

Cited by 76 publications

(89 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To expand upon the findings of the present study, we further plan to assess the beneficial effects of L-carnitine supplementation during chronic cigarette smoke exposure, a model of COPD in which emphysema is accompanied by chronic inflammation and airway remodelling [32,60]. It has been known for some time that oxidative stress following cigarette smoking is involved in many of the pathological processes underlying COPD [61] and, more recently, cigarette smoke has been shown to impair mitochondrial function [62].…”

Section: Discussionmentioning

confidence: 95%

“…H&E-stained lung tissue sections were analysed by design-based stereology using an Olympus BX51 light microscope equipped with the new Computer Assisted Stereological Toolbox (new-CAST, Visiopharm) as described previously [32]. Air space enlargement was assessed by calculating the mean linear intercept (MLI) across 30 random fields of view per lung.…”

Section: Quantitative Morphometrymentioning

confidence: 99%

See 1 more Smart Citation

Metabolomics screening identifies reducedL-carnitine to be associated with progressive emphysema

et al. 2016

Self Cite

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Quantitative Morphometrymentioning

confidence: 99%

Metabolomics screening identifies reducedL-carnitine to be associated with progressive emphysema

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Combining all of these findings, it suggests that Kupffer cells may play a significant role in initiating inflammatory responses in the liver and possibly outside of the liver. Again, there is little previous work on the role of tobacco products and ecigarette products on Kupffer cell health, however, similar cytokine release profiles have been observed after macrophage exposure to cigarette products (Hubeau et al, 2013;John-Schuster et al, 2014;Kubo et al, 2005;Pauwels et al, 2011;Shen et al, 2014).…”

Section: Cytokine Releasementioning

confidence: 91%

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Rubenstein

Hom

Ghebrehiwet

2015

Molecular Immunology

View full text Add to dashboard Cite

“…Consistent with increased levels of cytokines, lymphoid aggregates, previously associated with severe emphysema in human COPD lungs (40), were also detected in lungs from Hhip +/− mice. An increased number of lymphoid aggregates may contribute to the greater airspace enlargement observed in Hhip +/− mice as (i) lymphoid aggregate number and size correlate with emphysema severity in human COPD patients (41); (ii) activated T lymphocytes (which are present in lymphoid aggregates) not only secrete MMPs (42) that can promote lung destruction, but also induce greater MMP production by macrophages (43); (iii) B cells (also present in lymphoid aggregates) promote CS-induced emphysema in mice (44); and (iv) B-cell products (autoantibodies) have been linked to emphysema in CS-exposed mice and human COPD patients (45,46). Thus, Hhip may protect mice from spontaneous airspace enlargement in mice by inhibiting adaptive immunity (including lymphoid aggregates formation).…”

Section: Hhip Interacts With Gstp1 and Enhances Glutathione-conjugatingmentioning

confidence: 99%

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Lao

Jiang

Yun

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip+/−), we observed increased lung compliance and spontaneous emphysema in Hhip+/− mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip+/− vs. Hhip+/+ mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip+/− mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip+/− mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip+/− mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

show abstract

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

Abstract: Eickelberg O, Yildirim AÖ. Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD.

Cited by 76 publications

References 59 publications

Metabolomics screening identifies reducedL-carnitine to be associated with progressive emphysema

Metabolomics screening identifies reducedL-carnitine to be associated with progressive emphysema

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Contact Info

Product

Resources

About