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Club cells, also known as bronchiolar exocrine cells, and formerly known as Clara cells, are low columnar/cuboidal cells with short microvilli, found in the small airways ( bronchioles) of the lungs. Club cells are found in the ciliated simple epithelium. These cells may secrete glycosaminoglycans 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 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their se ...
s decrease. One of the main functions of club cells is to protect the bronchiolar epithelium. 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. They are also responsible for detoxifying harmful substances inhaled into the lungs. Club cells accomplish this with
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
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 differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
, 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 (EC 3.2.1.17, 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 glycosid ...
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 Cytochrome P450 4B1 is a protein that in humans is encoded by the ''CYP4B1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bi ...
, 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, which is believed to be responsible for cleaving the hemagglutinin surface protein of influenza A virus, thereby activating it and causing the symptoms of flu. When the l7Rn6 protein is disrupted in mice, these mice display severe
emphysema Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the a ...
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 cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
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

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 (german: Nationalsozialistische Deutsche Arbeiterpartei or NSDAP), was a far-right political party in Germany active between 1920 and 1945 that created and supported t ...
and used tissue taken from executed victims of
Nazi Germany Nazi Germany (lit. "National Socialist State"), ' (lit. "Nazi State") for short; also ' (lit. "National Socialist Germany") (officially known as the German Reich from 1933 until 1943, and the Greater German Reich from 1943 to 1945) was ...
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 European Respiratory Society and the American College of Chest Physicians) concluded that the continued use of Clara's
eponym An eponym is a person, a place, or a thing after whom or which someone or something is, or is believed to be, named. The adjectives which are derived from the word eponym include ''eponymous'' and ''eponymic''. Usage of the word The term ''epon ...
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.


See also

* cGMP-dependent protein kinase * List of medical eponyms with Nazi associations * Skatole * List of human cell types derived from the germ layers


References


External links

* *
Histology at ucsf.edu
{{Authority control Lung anatomy Surfactant secreting cells Animal cells Human cells Nazi human subject research