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- Lepzien, Rico, et al.
(författare)
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Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Pulmonary sarcoidosis is an inflammatory disease characterised by granuloma formation and heterogeneous clinical outcome. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells, which are poorly studied in sarcoidosis, despite their central role in inflammation.Objective To determine the role of pulmonary monocyte-derived cells and dendritic cells during sarcoidosis.Methods We performed in-depth phenotypic, functional and transcriptomic analysis of MNP subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. We followed the clinical development of patients and assessed how the repertoire and function of MNP subsets at diagnosis correlated with 2-year disease outcome.Results Monocytes/monocyte-derived cells were increased in blood and BAL of sarcoidosis patients compared to healthy controls. Interestingly, high frequencies of blood intermediate monocytes at time of diagnosis associated with chronic disease development. RNA sequencing analysis showed highly inflammatory MNPs in BAL of sarcoidosis patients. Furthermore, frequencies of BAL monocytes/ monocyte-derived cells producing TNF without exogenous stimulation at time of diagnosis increased in patients that were followed longitudinally. In contrast to alveolar macrophages, the frequency of TNFproducing BAL monocytes/monocyte-derived cells at time of diagnosis was highest in sarcoidosis patients that developed progressive disease.Conclusion Our data show that pulmonary monocytes/monocyte-derived cells are highly inflammatory and can be used as a predictor of disease outcome in sarcoidosis patients.
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| 2. |
- Rankin, Gregory D., et al.
(författare)
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Acute Exposure to Diesel Exhaust Increases Muscle Sympathetic Nerve Activity in Humans
- 2021
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diesel exhaust (DE) emissions are a major contributor to ambient air pollution and are strongly associated with cardiovascular morbidity and mortality. Exposure to traffic-related particulate matter is linked with acute adverse cardiovascular events; however, the mechanisms are not fully understood. We examined the role of the autonomic nervous system during exposure to DE that has previously only been indirectly investigated.Methods and Results: Using microneurography, we measured muscle sympathetic nerve activity (MSNA) directly in the peroneal nerve of 16 healthy individuals. MSNA, heart rate, and respiration were recorded while subjects rested breathing filtered air, filtered air with an exposure mask, and standardized diluted DE (300 µg/m3) through the exposure mask. Heart rate variability was assessed from an ECG. DE inhalation rapidly causes an increase in number of MSNA bursts as well as the size of bursts within 10 minutes, peaking by 30 minutes (P<0.001), compared with baseline filtered air with an exposure mask. No significant changes occurred in heart rate variability indices during DE exposure; however, MSNA frequency correlated negatively with total power (r2=0.294, P=0.03) and low frequency (r2=0.258, P=0.045). Heart rate correlated positively with MSNA frequency (r2=0.268, P=0.04) and the change in percentage of larger bursts (burst amplitude, height >50% of the maximum burst) from filtered air with an exposure mask (r2=0.368, P=0.013).Conclusions: Our study provides direct evidence for the rapid modulation of the autonomic nervous system after exposure to DE, with an increase in MSNA. The quick increase in sympathetic outflow may explain the strong epidemiological data associating traffic-related particulate matter to acute adverse cardiovascular events such as myocardial infarction.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02892279.
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