Club cells, also known as bronchiolar exocrine cells, are low columnar/cuboidal cells with short

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 ...

, found in the small airways (

bronchioles The bronchioles ( ) are the smaller branches of the bronchial airways in the lower respiratory tract. They include the terminal bronchioles, and finally the respiratory bronchioles that mark the start of the respiratory zone delivering air to t ...

) of the

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

s. They were formerly known as ''Clara cells''. Club cells are found in the ciliated simple epithelium. These cells may secrete

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...

s to protect the bronchiole lining. Bronchiolar cells gradually increase in number as the number of

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 decrease. One of the main functions of club cells is to protect the bronchiolar

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

. They do this by secreting a small variety of products, including club cell secretory protein uteroglobin, and a solution similar in composition to

pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by Type II cells, type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorption, adso ...

. They are also responsible for detoxifying harmful substances inhaled into the lungs. Club cells accomplish this with

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzymes found in their smooth endoplasmic reticulum. Club cells also act as a

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 ...

, multiplying and differentiating into ciliated cells to regenerate the bronchiolar epithelium.

Function

The respiratory bronchioles represent the transition from the conducting portion to the respiratory portion of the respiratory system. The narrow channels are usually less than 2 mm in diameter and they are lined by a simple cuboidal epithelium, consisting of ciliated cells and non-ciliated club cells, which are unique to bronchioles. In addition to being structurally diverse, club cells are also functionally variable. One major function they carry out is the synthesis and secretion of the material lining the bronchiolar lumen. This material includes glycosaminoglycans, proteins such as

lysozyme Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...

s, and conjugation of the secretory portion of IgA antibodies. These play an important defensive role, and they also contribute to the degradation of the mucus produced by the upper airways. The heterogeneous nature of the dense granules within the club cell's cytoplasm suggests that they may not all have a secretory function. Some of them may contain lysosomal enzymes, which carry out a digestive role, either in defense: Club cells engulf airborne toxins and break them down via their cytochrome P-450 enzymes (particularly CYP4B1, which is only present in the club cells) present in their smooth endoplasmic reticulum; or in the recycling of secretory products. Club cells are mitotically active. They divide and differentiate to form both ciliated and non-ciliated epithelial cells.

Clinical significance

Club cells contain

tryptase Tryptase () is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemagglu ...

, which is believed to be responsible for cleaving the

hemagglutinin The term hemagglutinin (alternatively spelt ''haemagglutinin'', from the Greek , 'blood' + Latin , 'glue') refers to any protein that can cause red blood cells (erythrocytes) to clump together (" agglutinate") ''in vitro''. They do this by bindin ...

surface protein of

influenza A ''Influenza A virus'' (''Alphainfluenzavirus influenzae'') or IAV is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. It is a pathogen with strains that infect birds and some mammals, as well as c ...

virus, thereby activating it and causing the symptoms of flu. When the l7Rn6 protein is disrupted in mice, these mice display severe

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 ...

at birth as a result of disorganization of the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

and formation of aberrant vesicular structures within club cells. Malignant club cells are also seen in bronchioalveolar carcinoma of the lung. Serum club cell proteins are used as a biomarker of lung permeability. Exposure to particulate air pollution may compromise the integrity of the lung epithelium and lead to rapid increase in epithelial barrier permeability, as reflected by increased serum club cell concentrations.

History

Name change

Club cells were previously called ''Clara cells'', as they were first described by Max Clara (1899–1966), in 1937. Clara was an active member of the

Nazi Party The Nazi Party, officially the National Socialist German Workers' Party ( or NSDAP), was a far-right politics, far-right political party in Germany active between 1920 and 1945 that created and supported the ideology of Nazism. Its precursor ...

and used tissue taken from executed victims of

Nazi Germany Nazi Germany, officially known as the German Reich and later the Greater German Reich, was the German Reich, German state between 1933 and 1945, when Adolf Hitler and the Nazi Party controlled the country, transforming it into a Totalit ...

for his research—including the work that led to his discovery of Clara cells. In May 2012, the editorial boards of most of the major respiratory journals (including the journals of the

American Thoracic Society The American Thoracic Society (ATS) is a nonprofit organization focused on improving care for pulmonary diseases, critical illnesses and sleep-related breathing disorders. It was established in 1905 as the American Sanatorium Association, and ...

, the

European Respiratory Society The European Respiratory Society, or ERS, is a non-profit organization with offices in Lausanne, Brussels and Sheffield. It was founded in 1990 in the field of respiratory medicine. The organization was formed with the merger of the Societas Eur ...

and the

American College of Chest Physicians The American College of Chest Physicians (CHEST) is a medical association in the United States consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, critical care medicine Intensiv ...

) concluded that the continued use of Clara's

eponym An eponym is a noun after which or for which someone or something is, or is believed to be, named. Adjectives derived from the word ''eponym'' include ''eponymous'' and ''eponymic''. Eponyms are commonly used for time periods, places, innovati ...

would be equivalent to honoring him; they therefore introduced a name-change policy, which went into effect beginning January 1, 2013. The term "Clara" was used parenthetically after "club cell" for a 2-year period, after which "Clara cell" and "Clara cell secretory protein" were conclusively replaced with "club cell" and "club cell secretory protein", respectively.

References

External links