The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration?

Hayman, Yvette A.; Sadofsky, Laura R.; Williamson, James D.; Hart, Simon P.; Morice, Alyn H.

Abstract

Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid laden macrophages (LLM) within the airway may indicate aspiration secondary to GOR. The proposed mechanism, that lipid droplets from undigested or partially digested food are aspirated leading to accumulation in scavenging macrophages led us to hypothesise that an activated population of LLM could interact with other immune cells to induce bronchial inflammation. To test this, we generated an in vitro model using differentiated THP-1 cells which were treated with a high fat liquid feed. Here we show that THP-1 cells can take up lipid from the high fat feed independent of actin polymerisation or CD36 dependent phagocytosis. These cells did not exhibit M1 or M2 polarisation. Gene array analysis confirmed over 8000 genes were upregulated by at least two fold following high fat exposure and IL-8 was the most upregulated gene. Pathway analysis revealed upregulation of genes known to be involved in chronic obstructive pulmonary disease (COPD) pathophysiology. We suggest that aspiration and macrophage phagocytosis may be important mechanisms in the aetiology of diseases such as COPD and cystic fibrosis which are characterised by high levels of IL-8 within the airways.

Citation

Hayman, Y. A., Sadofsky, L. R., Williamson, J. D., Hart, S. P., & Morice, A. H. (2017). The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration?. Ers Monograph, 3(1), 00026-2016. https://doi.org/10.1183/23120541.00026-2016

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2017
• Online Publication Date: Mar 20, 2017
• Publication Date: Mar 20, 2017
• Deposit Date: Feb 27, 2017
• Publicly Available Date: Mar 20, 2017
• Journal: ERJ open research
• Print ISSN: 2312-508X
• Electronic ISSN: 2312-5098
• Publisher: European Respiratory Society
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 1
• Article Number: 00026-2016
• Pages: 00026-2016
• DOI: https://doi.org/10.1183/23120541.00026-2016
• Keywords: Macrophages, Lipid laden macrophages, THP-1 cells, Reflux, COPD
• Public URL: https://hull-repository.worktribe.com/output/448909
• Publisher URL: http://openres.ersjournals.com/content/3/1/00026-2016
• Additional Information: Copy of article first published in: ERJ open research, 2017, v.3, issue1.