Club Cell
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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
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s. 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 ...
s to protect the bronchiole lining. Bronchiolar cells gradually increase in number as the number of goblet cells decrease. One of the main functions of club cells is to protect the bronchiolar
epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
. They do this by secreting a small variety of products, including club cell secretory protein
uteroglobin Uteroglobin, or blastokinin, also known as secretoglobin family 1A member 1 (SCGB1A1), is a protein that in humans is encoded by the ''SCGB1A1'' gene. SCGB1A1 is the founding member of the secretoglobin family of small, secreted, disulfide-bridged ...
, and a solution similar in composition to
pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic In chemistry, hydrophobicity is t ...
. They are also responsible for detoxifying harmful substances inhaled into the lungs. Club cells accomplish this with
cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes found in their
smooth endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough 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 o ...
, 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 glycoside ...
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 ''b ...
, 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 hemag ...
, which is believed to be responsible for cleaving the
hemagglutinin In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the ''Paramyxoviridae'' family. Hemagglutinins ar ...
surface protein of
influenza A '' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. Strains of all subtypes of influenza A virus have been isolated from wi ...
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 alve ...
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 ins ...
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 Max Clara (12 February 1899, Völs am Schlern, Austro-Hungary – 13 March 1966, Munich) was a German anatomy, anatomist and Nazi Party member, who conducted research on the corpses of executed prisoners. Biography Early life 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 politics, far-right political party in Germany active between 1920 and 1945 that crea ...
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 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 ch ...
, 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 Euro ...
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 cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle ...
*
List of medical eponyms with Nazi associations This article lists medical eponyms which have been associated with Nazi human experimentation or Nazi politics. While normally eponyms used in medicine serve to honor the memory of the physician or researcher who first documented a disease or pione ...
*
Skatole Skatole or 3-methylindole is an organic compound belonging to the indole family. It occurs naturally in the feces of mammals and birds and is the primary contributor to fecal odor. In low concentrations, it has a flowery smell and is found in seve ...
*
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corticotro ...


References


External links

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