Introduction and objectives The alveolar macrophage (AM) is a key player in orchestrating the inflammatory response to inhaled pathogens and environmental toxins. DEP causes the release of monocytes from the bone marrow, and during chronic inflammation, macrophages mature continuously from infiltrating monocytes. There are no studies investigating the chronic effects of DEP on monocytes and actions of DEP on neutrophils are unclear. We investigated how DEP modulate neutrophil and monocyte function and macrophage differentiation.
Methods Monocytes and neutrophils were obtained from healthy volunteers by density gradient centrifugation and negative magnetic selection. Monocyte-derived macrophages (MDMs) were generated in the presence or absence of DEP. Apoptosis and cell loss of MDMs were assessed by microscopy, propidium iodide positivity and alamar blue reduction assays. Killing assays of Streptococcus pneumoniae were performed. Cytokine generation in response to varied TLR agonists was assessed by ELISA and surface marker expression of receptors including TLRs, and CD14 was measured by FACS.
Results Monocytes and MDMs avidly phagocytosed DEP but neutrophils neither phagocytosed DEP, or markedly responded to DEP. However, chronic exposure to DEP in vitro had a detrimental effect on monocytes, with marked enhancement of apoptosis and cell loss. Despite this, the ability to kill an important respiratory pathogen S pneumoniae was preserved. Cytokine generation to TLR agonists was reduced, and this phenotype was associated with a reduction in CD14 surface marker expression.
Conclusions DEP directly activate monocytes but not neutrophils, and chronic exposure may have detrimental effects on the host by enhancing loss of monocytes recruited to the airways and modulating aspects of the inflammatory response to pathogens.
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