Lung Cell Biology

Professor Terry Tetley, Head of Group

The Lung Cell Biology group programme of research focuses on the mechanisms underlying the innate immune response of the alveolar unit to inhaled toxicants. With over thirty years expertise in isolation and culture of primary human lung cells, the group have established a number of in vitro models of the respiratory unit to study the effects of microbial infection, cigarette smoke, air pollution and most recently, engineered nanoparticles.

Microbial Infection and Smoking
Nanotoxicology

Microbial Infection and Smoking

Confocal microscopy image of Toll-like receptor 4 expression (green) by human alveolar macrophages. Nuclei are stained blue.

Over 50% of COPD patients have persistent microbial colonisation of the lower respiratory tract. Understanding the mechanisms underlying the innate immune response of the alveolar unit to bacterial infection is therefore important for identification of future therapeutic targets. Our studies have focused on TLR expression and their signalling pathways in the alveolar unit and their involvement in the innate immune response. We have demonstrated that macrophages and epithelial cells work together to release a range of mediators that orchestrate the magnitude and profile of the inflammatory response (1); of particular interest is the finding that the alveolar epithelium is a crucial link in the recruitment and specific activation of dendritic cells, which are important in bridging the innate and adaptive immune responses (2).

NanotoxicologyTime lapse movie showing phagocytosis of fluorescent particles (green) by human alveolar macrophages.

We have obtained significant funding from government agencies, research councils and industry to investigate the adverse health effects of engineered nanoparticles, born out of the urgent need for toxicological testing of engineered nanoparticles in light of the recent explosion in their development and use in everyday consumer products.

It is likely that any adverse effects of inhaled engineered nanoparticles may be initiated in the peripheral alveolar region of the lung, as this is the primary site of deposition for inhaled nanoparticles.

Confocal microscopy image of nanoparticle uptake (green) by human alveolar type I epithelial cells (actin cytoskeleton stained red)

Amongst the in vitro models that we use is a unique immortalised alveolar type 1 epithelial cell line that was generated in-house (3).

This cell type covers over 95% of the alveolar surface and is thus a primary target of inhaled nanoparticles. Using this cell line, we have investigated the mechanisms underlying nanoparticle uptake, focusing on endocytic pathways and direct nanoparticle-membrane interactions.

In addition, we are investigating the mechanism underlying the pro-inflammatory and cytotoxic effects of nanoparticle exposure. Our studies are focusing on the effect of nanoparticle exposure on MAP kinase activation, caspase activity and subsequent cytokine and chemokine release.