Abstract
CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function.
Highlights
Chronic beryllium disease (CBD) develops in up to 16% of individuals exposed to beryllium (Be) and is characterized by granulomatous inflammation and the accumulation of CD4+ T cells in the lung [1]
In the present work we have demonstrated that the circulating CD14dimCD16+ monocytes, which represent a pro-inflammatory subpopulation, are present at a lower frequency in peripheral blood mononuclear cells (PBMC) than the lung of CBD and beryllium sensitized Non-smoker (BeS-NS) patients
We have shown that alveolar macrophages (AMs) of CBD and beryllium sensitization (BeS)-NS display an activated cell surface phenotype with higher frequencies of the markers CD40, CD86 and HLA-DR in contrast to AMs of healthy subjects (HS) and BeS smokers (BeS-S)
Summary
Chronic beryllium disease (CBD) develops in up to 16% of individuals exposed to beryllium (Be) and is characterized by granulomatous inflammation and the accumulation of CD4+ T cells in the lung [1]. Studies show that Be persists within the lungs of individuals many years after exposure has ceased [4], suggesting a failure to clear Be antigen from the lungs This retention of Be may perpetuate an ongoing Be-specific immune response in CBD and/ or progression from BeS to CBD. Previous studies have shown that the number of CD14+CD16+ monocytes are expanded during severe infectious and inflammatory conditions, such as Rheumatoid arthritis (RA) [10], tuberculosis [11], asthma [12] and sarcoidosis [13] These monocytes have been implicated in the pathogenesis of several inflammatory diseases, such as RA as they produce higher levels of tumor necrosis factor-α (TNF- α) and IL-1β and preferentially differentiate into macrophages [14]. This has not been investigated in patients with CBD
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