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2620224 
Journal Article 
Abstract 
Diesel exhaust particles alter monocyte differentiation in vitro 
Chaudhuri, N; Piddock, K; Donaldson, K; Parker, L; Sabroe, I 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1032 
English 
WOS:000208771000033 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Introduction and Objectives: The alveolar macrophage (AM) represents the first line of defense and is a key player in orchestrating the inflammatory response. DEP has been shown to cause the release of monocytes from the bone marrow. There are no studies to date investigating the chronic effects of DEP on monocytes that have been recruited to the airways and their subsequent differentiation into macrophages. We therefore hypothesised that repetitive DEP exposure would drive the monocyte to differentiate into a macrophage exhibiting an M1 inflammatory phenotype with the production of proinflammatory mediators that would contribute to the development of chronic inflammation.

Methods: Freshly purified human monocytes avidly phagocytosed diesel particles. Monocytes were then cultured with macrophage colony stimulating factor (M-CSF) for the first 3-4 days, in the presence or absence of 50 µg/ml DEP. At day 7 a number of functional assays were performed. Apoptosis and cell loss was assessed by direct microscopy, propidium iodide positivity and an alamar blue reduction assay. Killing assays of Streptococcus pneumoniae were performed as previously described. Cytokine generation in response to varied TLR agonists after 24 hour stimulation was assessed by ELISA and surface marker expression of TLR2, TLR4, CD11b, CD14 and HLA-DR was performed by flow cytometry.

Results: Contrary to our hypothesis, we demonstrated that chronic exposure to DEP in vitro has a detrimental effect on monocytes with the resultant cell loss and enhancement of apoptosis. Despite this the ability to kill an important respiratory pathogen, S. pneumoniae is preserved. This is coupled with a suppression of CXCL8, TNF-α and RANTES generation in response to varied TLR agonists, in particular LPS and Pam3CSK. Further exploration associated this phenotype with a reduction in CD14 surface marker expression.

Conclusions: Our data have suggested that chronic DEP exposure would have detrimental effects on the host by enhancing loss of monocytes recruited to the airways and potentially reducing the inflammatory response to pathogens. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010