Introducing the pneumocytes
Breathe in, breathe out! We breathe 24x7x365 without even realizing that the lungs are doing a significant amount of work in helping us breathe and serving their main function: gas exchange. The mammalian lung is an excellent example where “form follows function” meaning its function is dependent on its shape. The alveoli are the important part of the mammalian lung where most of the gas exchange takes place. Their unique grape-like anatomy contributes to an increased surface area for easy exchange and transport of oxygen to the blood. The alveolar lumen is furnished with a mosaic of epithelium called alveolar epithelial cells (AECs) which are also known as pneumocytes (1).
Responsibilities of pneumocytes
95% of the alveolar surface is covered with thin squamous cell extensions of type I epithelial cells (type I pneumocytes) and the rest belongs to single cuboidal type II epithelial cells (type II pneumocytes). Type I cells are mainly involved in the maintenance of air-blood barriers and prevent leakage of fluid into the alveolar space (2). Type II cells are specialized cells that produce pulmonary surfactants (lipid-protein complex) which reduce surface tension in the lung’s air-liquid interface (ALI) (3). The lamellar bodies (LBs) are the secretory organelles and a characteristic feature of type II pneumocytes which act as an intracellular storage for the surfactants. These LBs release surfactants at the end of expiration reducing surface tension and thus prevent alveolar collapse, medically known as atelectasis (4). The numerical relationship between type I and type II is 1:2 (5). Several studies (6,7) have been carried out to mimic the complex pulmonary microarchitecture in in vitro platforms with the caveat that lung cells lose their phenotypic characteristics (8) in long-term cultures.
Type I and type II pneumocytes go hand-in-hand
Ever seen a pair of identical twins where the one is smarter than the other and always protects the other one? Type I and type II pneumocytes are quite the same. Being dominant cell types of the lung alveoli, they are an easy target for most of the toxic exposures. The type I cells are very susceptible to structural damage as a result of the toxic injury, on the other hand type II cells stay ahead and aim to keep the structural integrity of the alveolar epithelium intact for proper functioning of the lung. Type II cells express a range of metabolic processes in response to acute and chronic exposures whereas there is no defined metabolic activity for type I cells. A better knowledge on toxicant induced lung inflammation will be helpful in identifying the metabolic responses for type I pneumocytes (9). Type II pneumocytes have a very interesting capability of forming alveolospheres which can further differentiate into organoids containing both type I and type II pneumocytes (AECs) (10).
Response of pneumocytes to various lung injuries
Alveolar epithelium is the most vulnerable segment of a mammalian lung. It is exposed to both air and blood borne toxicants. Inhalation of a dangerous gas such as mustard gas or aspiration of a caustic solution, both can cause severe necrotic damage as well as exfoliation of the alveolar epithelium. Following the injury, type II cells start proliferating in an effort to repair the structure of the epithelium with immediate release of surfactants. Proliferation of type II cells is often followed by an inflow of migratory inflammatory cells into the alveoli to help with the epithelium maintenance. If the damage is mild, type II cells transform into type I cells and the immune components are subsided. In case of scarring or excessive damage, type II cells continue to proliferate and restore the epithelium structure which often leads to chronic alveolar irritation. This condition is characterised by continued inflammation of the alveoli wall and is identified as chronic interstitial pneumonia. Type I pneumocytes are specifically damaged in pulmonary edema, a condition in which the air-blood barrier is compromised and fluid build up starts in the lung leading to difficulty in breathing. Type I cells are easily attacked by toxicants such as NO2, SO2, H2S, and 3-methylindole, and often result in alveolar edema (2). Epithelial barriers regulate the passage between air-blood and air-liquid interface, and serve as a significant defense system against external substances. Both in vivo and in vitro models are required to gain a better understanding of the lung pathology such as infection, inflammation, cancer and other pulmonary diseases (11).
Recognizing and appreciating the labs working in this space
- Beers Lab, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. https://www.med.upenn.edu/mfbeerslaboratory/
- Lung development and regeneration Lab, Mayo Clinic, Rochester, Minnesota, USA. https://www.mayo.edu/research/labs/lung-development-regeneration/overview Twitter: @MayoClinic
- The Katzen Lab, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. https://www.med.upenn.edu/katzen-lab/
- Kim Laboratory, Boston’s Children Hospital, Boston, Massachusetts, USA. https://www.childrenshospital.org/research/labs/kim-laboratory-research
- Bridges Laboratory, National Jewish Health, Denver, Colorado, USA. https://www.nationaljewish.org/research-science/research-programs/department-of-medicine/research-laboratories/bridges-laboratory/overview
- Jichao Chen Laboratory, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. https://www.mdanderson.org/research/departments-labs-institutes/labs/jichao-chen-laboratory.html
- AlveoliX, Bern, Switzerland. https://www.alveolix.com/
- SynVivo, Huntsville, Alabama, USA. https://www.synvivobio.com/
- Noble Research Lab, Cedars Sinai Medical Center. Los Angeles, California, USA. https://www.cedars-sinai.edu/research-education/research/labs/noble.html
- Laboratory for Lung Development and Research, Riken Center for Biosystems Dynamic Research, Hyogo, Japan. https://www.riken.jp/en/research/labs/bdr/lung_dev/index.html
References
- Knudsen, Lars, and Matthias Ochs. “The micromechanics of lung alveoli: structure and function of surfactant and tissue components.” Histochemistry and cell biology vol. 150,6 (2018): 661–676. doi:10.1007/s00418–018–1747–9
- Jack R. Harkema, Kristen J. Nikula, Wanda M. Haschek, Chapter 14 — Respiratory System, Editor(s): Matthew A. Wallig, Wanda M. Haschek, Colin G. Rousseaux, Brad Bolon, Fundamentals of Toxicologic Pathology (Third Edition), Academic Press, 2018, Pages 351–393, ISBN 9780128098417, https://doi.org/10.1016/B978-0-12-809841-7.00014-9.
- Cerrada, Alejandro et al. “Pneumocytes Assemble Lung Surfactant as Highly Packed/Dehydrated States with Optimal Surface Activity.” Biophysical journal vol. 109,11 (2015): 2295–306. doi:10.1016/j.bpj.2015.10.022
- Daniels, Christopher B, and Sandra Orgeig. “Pulmonary surfactant: the key to the evolution of air breathing.” News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society vol. 18 (2003): 151–7. doi:10.1152/nips.01438.2003
- Crapo, J D et al. “Cell number and cell characteristics of the normal human lung.” The American review of respiratory disease vol. 126,2 (1982): 332–7. doi:10.1164/arrd.1982.126.2.332
- Horváth, Lenke et al. “Engineering an in vitro air-blood barrier by 3D bioprinting.” Scientific reports vol. 5 7974. 22 Jan. 2015, doi:10.1038/srep07974
- Fu, Anchen et al. “Dynamic tissue model in vitro and its application for assessment of microplastics-induced toxicity to air-blood barrier (ABB).” Biosensors & bioelectronics vol. 246 (2024): 115858. doi:10.1016/j.bios.2023.115858
- Lee, Diane Frances et al. “Isolation and characterisation of alveolar type II pneumocytes from adult bovine lung.” Scientific reports vol. 8,1 11927. 9 Aug. 2018, doi:10.1038/s41598–018–30234-x
- L.-Y. Chang, J.D. Crapo, P. Gehr, B. Rothen-Rutishauser, C. Mühfeld, F. Blank, 8.04 — Alveolar Epithelium in Lung Toxicology*, Editor(s): Charlene A. McQueen, Comprehensive Toxicology (Second Edition), Elsevier, 2010, Pages 59–91, ISBN 9780080468846, https://doi.org/10.1016/B978-0-08-046884-6.00904-0.
- Cunniff, Brian et al. “Lung organoids: advances in generation and 3D-visualization.” Histochemistry and cell biology vol. 155,2 (2021): 301–308. doi:10.1007/s00418–020–01955-w
- Nossa, Roberta et al. “Breathing in vitro: Designs and applications of engineered lung models.” Journal of tissue engineering vol. 12 20417314211008696. 28 Apr. 2021, doi:10.1177/20417314211008696
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The League of Extraordinary Cell types
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