How our lungs regenerate after inhaling airborne particulates and microplastics
The project entitled “Mechanisms of damage formation and its regeneration caused by particulate matter and microplastics from air pollution in a model of acute and chronic lung injury” is funded under the OPUS 25 National Science Center scheme.
Health impact of air pollution
Pollution of the environment, including the air, is an important factor affecting public health. Assessment of the impact of air pollution on our health and on the functioning of the respiratory system is currently the subject-matter of extensive research.
According to the World Health Organization, 4.2 million people worldwide die each year as a consequence of air pollution (2019 data). It has been proven that continuous exposure to air pollutants:
- Is a hazard even to healthy individuals,
- Strongly increases the incidence and mortality rates for cardiovascular and respiratory diseases, and the everity of lung diseases.
The potential negative health effects of inhaling airborne particulate and dust depend on the particle size and shape and the chemical, physical and biological properties of the particulate matter. It should be considered that the suspended particulate concentration and composition varies between regions, conditional upon multiple natural and anthropogenic factors such as its source, weather conditions, or geography.
Characteristics of suspended particulates
The majority of air pollutants in densely populated areas consists of particles generated in the process of incinerating plant biomass and coal, the most popular energy materials used for residential heating. Other sources of air pollution include combustion engine vehicles and the industry, emitting heavy metal contaminants to the atmosphere.
Airborne particles are characterized on the basis of their aerodynamic diameter. There is a distinction of PM (particulate matter) with aerodynamic diameters ranging from 10 μm to 2.5 μm (PM10); fine particles <2.5 μm (PM2,5), and ultrafine particles <0.1 μm (PM0,1).
Respiratory epithelium’s response to airborne particulate exposure depends on the sizes of inhaled particles. PM10 particles can penetrate the respiratory system, yet most of them are retained in the mucous layer and eliminated through respiratory clearance and macrophages. It should be noted that the largest airborne particles have an additional negative effect on tissues as carriers of heavy metals, toxins, biological load and other organic and inorganic components bound to their surfaces. Still, most research projects focus on the so-called respirable fraction, i.e. PM2.5, which is considered the most harmful.
Airborne fine particles represent more than 80% contaminants inhaled in the respiratory system and are capable of penetrating deeply, causing a series of biological reactions that lead to localized inflammation and lung injury.
Characteristics of microplastics
Another important component of air pollution, which has been broadly discussed recently, are microplastic fibers. Yearly production output of plastic continues to increase, reaching 390.7 million tons in 2021. 80% of plastic waste is deposited in landfills or in the natural environment where water, UV radiation and biological metabolism causes their fragmentation to microplastic (1 µm to 5 mm long) and nanoplastic fibers (1 µm to 100 nm).
As microplastic particles are insoluble in water, they are commonly discovered in marine environments, underground water, farmland ecosystems, food and drinking water. It has been demonstrated recently that a large proportion of tiny microplastic fibers will be suspended in the air and carried by wind at large distances, to be then inhaled and accumulated in the lungs. The specific mechanisms of chronic accumulation of microplastics in the airways are not yet properly recognized.
The protective function of the respiratory tract
Respiratory epithelium is the first point of contact between the body and the outside environment. It performs its protective function through multiple functional and morphological mechanisms that enables it to capture, treat and neutralize some of the inhaled pollutants. This response comprises:
- a layer of surfactant (lipid and protein substance) lining and protecting the alveoli;
- function of ciliated epithelium;
- highly phagocytic macrophages on the luminal side of pulmonary epithelium;
- presence of non-permeable junctions between epithelial cells;
- dendritic cells as specialized cells presenting antigen within and at the base of the epithelium and basal membrane;
- active localized inflammatory response initiated by the epithelium. The respiratory epithelial barrier is maintained and regulated by a matrix of intercellular junctions, including tight junctions and adhesive junctions.
Such versatile functions of the epithelium are delivered by its complex structure. There are multiple types of healthy respiratory epithelium, the most common of which are basal cells, ciliated cells, goblet cells, while the less common types include ionocytes, chemosensory cells (Tuft cells), club cells (formerly Clary cells), and neuroendocrine cells.
Due to its function, respiratory epithelium is adapted to respond to acute localized injuries (caused by bacteria, viruses or toxic substances) as well as chronic ones (caused by prolonged harmful stimulation, e.g. with tobacco smoke, chronic inflammation), characterized by loosening of interepithelial junctions and breaking their integrity as a result. Following an injury, the epithelium activates numerous recovery and regenerative mechanisms such as migration of basal cells, followed by their proliferation and differentiation into other types of epithelial cells. It has been demonstrated that activation of epidermal growth factor receptor (EGFR) by its ligands: EGF and transforming growth factor alpha (TGF-α) accelerates the recovery of respiratory epithelium.
As a consequence of prolonged exposure to harmful factors, recovery process may be insufficient or impaired. Permanent exposure to air pollution during the injury and the recovery process may therefore increase EGFR activity via matrix metalloproteinase-9 (MMP-9), causing inadequate reconstruction of respiratory epithelium.
Frequent injuries and inadequately controlled epithelium recovery processes lead to its restructuring: epithelial metaplasia and hypertrophy. These lesions may strongly interfere with inborn immune functions within the respiratory tract or lead to lung function impariment: extensive injury to small airways reduces the diffusion capacity and affects lung function, as a pathophysiology element of multiple lung diseases, such as chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis.
About the project
The purpose of the project entitled “Mechanisms of damage formation and its regeneration caused by particulate matter and microplastics from air pollution in a model of acute and chronic lung injury”, pursued at WUM Clinical Department of Internal Medicine, Pneumonology and Allergology, will be the characterization and comparison of biological processes following exposure to air pollution and microplastics in acute and chronic respiratory epithelium damage, as well as the study of recovery mechanisms in the process of tissue healing during stimulation with airborne particulate matter and microplastic fibers.
These purposes will be accomplished using 3D in vitro model of acute and chronic damage to epithelium containing co-cultures of macrophages and bronchial epithelium cells. The models will be physically wounded and the cells’ regenerative capacity will be assessed in cultures after airborne particulate and microplastic fibers exposure.
The assumption of the study hypothesis is that the negative effect of air pollution is correlated to structural changes of respiratory epithelium, and the healing process in damaged epithelium in the presence of air pollution particles is different for acute and chronic lung failure. Respiratory epithelium dysfunctions caused by chronic damage increase the epithelial permeability and enhance the toxic effect of air pollution.
Characteristics of epithelial response processes to airborne pollutants will improve our awareness of the influence of environmental pollution on the pathobiology of respiratory conditions, while it may also be a starting point in the search for new therapeutic targets, particularly aggravated asthma and COPD caused by air pollution.
Edit and fot.: Communication and Promotion Office