Airway basal cells are found deep in the
respiratory epithelium
Respiratory epithelium, or airway epithelium, is ciliated pseudostratified columnar epithelium a type of columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways ...
, attached to, and lining the
basement membrane
The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...
.
Basal cells are the
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s or progenitors of the airway epithelium and can
differentiate to replenish all of the epithelial cells including the ciliated cells, and secretory
goblet cell
Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, secre ...
s.
This repairs the protective functions of the epithelial barrier.
Basal cells are cuboidal with a large nucleus, few organelles, and scattered microvilli.
Basal cells are the first cells to be affected by exposure to cigarette smoke. Their disorganisation is seen to be responsible for the major airway changes that are characteristic of
COPD
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
.
Structure

Basal cells are cuboidal, with a large
nucleus, few
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...
s, and scattered
microvilli
Microvilli (: microvillus) are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, cellula ...
. Basal cells are attached to, and line the
basement membrane
The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...
.
The numbers of basal cells are highest in the large airways and become increasingly decreased in the smaller airways. Their percentage in the trachea is 34%, in the large bronchi 27%, and 10% in the larger of the bronchioles.
Basal cells can express a number of different receptors, notably
EGFR.
Basal cell derived precursors are found as intermediate cells (also known as parabasal, or indetermined cells) between the basal cells and the differentiated cells.
Function
Basal cells are the
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s, or progenitors of all the cells in the respiratory epithelium. The ciliated cells and secretory cells that form the epithelial barrier, and function in
mucociliary clearance
Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator describes the self-clearing mechanism of the respiratory tract, airways in the respiratory system. It is one of the two protective processes for the lungs in removi ...
, are terminally differentiated meaning that they cannot self-renew. These cells are vulnerable to damage and the basal cells can replace damaged cells by differentiation.
Typically the airway epithelium turns over fairly slowly with the basal cells in a quiescent state, and just a few intermediate cells being seen.
In response to damage to the differentiated cells, or to stress caused by smoking, the basal cells become active, proliferate, and form clonal patches, and the numbers of intermediate cells increase.
When activated the basal cells acquire damage-associated phenotypes to enable differentiation to the particular cell type that has been damaged.
The intermediate cells differentiate under the control of
FOXJ1 into ciliated cells; and into secretory cells under the control of Notch signalling, and the transcription factors SPDEF and
FOXA3.
The regeneration of cells can be normal or in the case of smokers the regeneration may be of altered histologic phenotypes.
Basal cells can also provide a defence function upregulating innate immune mediators such as RNase7, an
antimicrobial protein.
RNase7, mediates tissue repair, and the production of inflammatory
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s induced either by tobacco smoke, or by microbial pattern recognition. This is seen as a possible defence response of basal cells to injury that would be associated with microbial attack.
The response requires signalling via EGFR, which is highly expressed in basal cells.
Other innate immune mediators include
beta-defensin 2, and
lipocalin-2; pro-inflammatory
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s,
interleukin
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s
IL6, and
IL8; and
chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...
CCL20.
Dysfunction
Following injury to airway epithelium, the basal cells can become infected by the respiratory
syncytial virus. When this happens the basal cell can be skewed to favour the differentiation of mucus-producing (secretory
goblet cell
Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract. The goblet cells mainly use the merocrine method of secretion, secre ...
s) over that of ciliated cells. The normal ratio of ciliated cells to secretory cells is 10 to 1, and this is highly controlled throughout most of the respiratory tree.
When this ratio is upset in this way, the effect is of generating the mucus hyperplasia associated with a number of respiratory diseases, due to the insufficient ciliary action needed for mucociliary clearance. The release of antimicrobials may occur as a second-line defence with cell differentiation.
Disruption of the tight-junction barrier is a common feature of
asthma
Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
, and of smoking-related
respiratory disease
Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, ...
s. The persistent activation of the innate immune response in basal cells, may contribute to the characteristic chronic
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
seen in these disorders.
Clinical significance
The hyperplasia of airway basal cells is the earliest indication of smoking-related abnormality in the lung.
This is followed by shortened cilia, loss of ciliated cells, mucous cell hyperplasia, and loss of cell junctions giving a leaky epithelial barrier. With persistent stress from smoking, the basal cells become disarranged and lose their regenerative ability needed to repair the barrier. The disorganised basal cells are seen to be responsible for the major airway changes that are characteristic of
COPD
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
, and with continued stress can undergo a malignant transformation. Studies have shown that the initial development of
emphysema
Emphysema is any air-filled enlargement in the body's tissues. Most commonly emphysema refers to the permanent enlargement of air spaces (alveoli) in the lungs, and is also known as pulmonary emphysema.
Emphysema is a lower respiratory tract di ...
is centred on the early changes in the airway epithelium of the small airways.
Basal cells become further deranged in a smoker’s transition to clinically defined COPD.
Basal cell dysfunction causes the overproduction and secretion of mucus, and decreased
mucus clearance that leads to the characteristic features of
mucus hypersecretion
Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...
, and
productive cough
A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ...
of chronic bronchitis and chronic obstructive pulmonary disease (COPD).
Mucus accumulation in COPD influences lung function, quality of life, exacerbations, hospital stays, and mortality, for the worse.
In response to a viral infection the basal cells may be activated to produce an increased production of
Interleukin 33 and mucins, and these activated cells may become a long-lived population that promote chronic inflammation;
as can influence the occurrence of an
exacerbation of COPD.
References
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Epithelium