The role of social determinants in the potential for inhaled microplastic pollution to affect macrophage energy metabolism
Lead Researcher: Dr Stephanie Wright
Supported by the Social, Genetic & Environmental Determinants of Health (SGE) Theme
Tiny plastic particles, called microplastics, are everywhere, including in the air we breathe. We’re worried about how these particles might harm our health, especially our lungs.
How Microplastics Might Harm Us:
- Disrupting Cell Energy: Microplastics can interfere with how our cells produce energy, which is crucial for their proper function.
- Weakening Immune Response: When this energy disruption occurs in immune cells, it can weaken our immune system, making us more susceptible to respiratory diseases like asthma.
Our Research: We’re studying how microplastics in indoor air, especially in homes, affect our health. We’ll focus on how these particles impact our immune cells and their ability to fight off infections.
Our Approach:
- Modelling Indoor Air: We’ll create particle models of indoor air in different types of homes, from wealthy to poor, to simulate real-world exposure.
- Testing Cell Energy: We’ll use a special tool called Seahorse which measures oxygen and acid in the liquid outside of the cells, to quantify how microplastics affect the way in which mitochondria use oxygen to create energy in immune cells.
- Analysing Immune Response: We’ll examine how these changes in cell energy impact the immune system’s response to inflammation by quantifying proteins involved in the immune response.
Our Goal: By understanding these effects, we can provide recommendations to reduce exposure to harmful microplastics and improve indoor air quality, leading to better health outcomes.
How Oxygen Levels Affect Immune Cells and Lung Damage in Chronic Obstructive Pulmonary Disease (COPD)
Lead Researcher: Katharine Lodge
Supported by the Respiratory Theme
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lungs with poor life expectancy. Approximately 6000 cases/year are diagnosed in the UK. The cause of IPF is unknown but we understand that white blood (immune) cells can infiltrate the lungs and damage the delicate structure, causing irreversible scarring (fibrosis). Because fibrosis destroys gas-exchanging regions of the lungs, IPF patients experience increasingly low oxygen levels (hypoxia) in the lungs and blood. I have previously shown that, even in healthy lungs, hypoxia increases the influx of immune cells, e.g. neutrophils, which can cause lung damage. I have also shown that healthy neutrophils exposed to hypoxia release many toxic proteins, which further increases their lung damage capacity. However, the impact of hypoxia on these and other immune cells in IPF is unknown.
I predicted that in IPF, hypoxia affects immune cell type and/or function, which contributes to disease progression. I therefore studied how different oxygen levels affect immune cells in IPF to try and see whether changes in type or function cause worsening lung damage. I focused particularly on neutrophils as I have already shown that hypoxia may induce detrimental functional changes in this cell type.
Using blood samples from IPF patients and healthy volunteers, I showed that neutrophils from IPF patients express different genes than cells from healthy controls and this may be a reason why their activity is increased in lung disease.
I next compared the diversity and behaviour of IPF versus healthy immune cells. These experiments showed that neutrophils from patients with IPF have different physical properties than neutrophils from healthy people without lung disease. Neutrophils from IPF patients are larger and stiffer and therefore may more easily become trapped in very small blood vessels in the lung. To test this, I have developed a new laboratory model to examine how easily neutrophils can travel through a chip that simulates lung blood vessels.
I next tested some chemicals that can inhibit certain signal pathways in neutrophils, including those that are switched on by hypoxia. Although the specific oxygen-sensing inhibitors did not change how active neutrophils were, a different inhibitor that controls the pathway that neutrophils use to secrete toxic proteins showed that this process could be reduced under hypoxia in healthy cells. I will now test this inhibitor in IPF patient cells.
Overall, this project has shown that immune cells, specifically neutrophils, in patients with IPF behave differently and have different DNA signatures. I have found an inhibitor that might be able to reduce the overactivation of these neutrophils. I will now test this using cells from patients with IPF to see if the new inhibitor has the potential to reduce lung damage.