| Goblet cell | |
|---|---|
 Schematic illustration of a goblet cell in close up, illustrating different internal structures of the cell. | |
 Transverse section of avillus, from the humanintestine. X 350. a.Basement membrane, here somewhat shrunken away from the epithelium. b.Lacteal. c.Columnar epithelium. d. Its striated border. e.Goblet cells. f.Leucocytes in epithelium. f'. Leucocytes below epithelium. g.Blood vessels. h.Muscle cells cut across. | |
| Details | |
| System | Respiratory system |
| Shape | Simple columnar |
| Function | Mucin-producingepithelial cells |
| Identifiers | |
| Latin | exocrimohsinoctus caliciformis |
| MeSH | D020397 |
| TH | H3.04.03.0.00009, H3.04.03.0.00016, H3.05.00.0.00006 |
| FMA | 13148 |
| Anatomical terms of microanatomy | |
Goblet cells aresimple columnar epithelial cells that secrete gel-formingmucins, likemucin 2 in the lower gastrointestinal tract, andmucin 5AC in the respiratory tract.[1] The goblet cells mainly use themerocrine method of secretion, secreting vesicles into a duct, but may useapocrine methods, budding off their secretions, when under stress.[2] The termgoblet refers to the cell's goblet-like shape. The apical portion is shaped like a cup, as it is distended by abundant mucus laden granules; its basal portion lacks these granules and is shaped like a stem.
The goblet cell is highly polarized with the nucleus and other organelles concentrated at the base of the cell and secretory granules containing mucin, at the apical surface.[1] The apical plasma membrane projects shortmicrovilli to give an increased surface area for secretion.[3]
Goblet cells are typically found in therespiratory,reproductive andlower gastrointestinal tracts and are surrounded by other columnar cells.[1]Biased differentiation ofairway basal cells in therespiratory epithelium into goblet cells plays a key role in the excessive mucus production, known asmucus hypersecretion, seen in many respiratory diseases, includingchronic bronchitis andasthma.[4][5]
Goblet cells are found scattered among theepithelial lining oforgans, such as theintestinal andrespiratory tracts.[6] They are found inside thetrachea,bronchi, and largerbronchioles in the respiratory tract,small intestines, thelarge intestine, andconjunctiva in the uppereyelid. In theconjunctiva goblet cells are a source of mucin intears and they also secrete different types of mucins onto theocular surface. In thelacrimal glands, mucus issynthesized byacinar cells instead.[7]
Goblet cells aresimple columnar epithelial cells, having a height of four times that of their width. Thecytoplasm of goblet cells tends to be displaced toward the basal end of the cell body by the largemucin granules, which accumulate near theapical surface of the cell along theGolgi apparatus, which lies between the granules and thenucleus. This gives the basal part of the cell abasophilic staining because ofnucleic acids within the nucleus andrough endoplasmic reticulum staining withhematoxylin. Mucin within the granules stains pale in routinehistology sections, primarily because thesecarbohydrate-rich proteins are washed out in thepreparation of microscopy samples. However, they stain easily with thePAS staining method, which colours them magenta.[8][9]
Inmucicarmine stains, deep red mucin is found within goblet cell bodies. Goblet cells can be seen in the examples below as the larger, more pale cells.
The main role of goblet cells is to secretemucus in order to protect themucous membranes where they are found. Goblet cells accomplish this by secretingmucins, largeglycoproteins formed mostly bycarbohydrates. The gel-like properties of mucins are given by itsglycans (bound carbohydrates) attracting relatively large quantities of water.[10] On the inner surface of the human intestine, it forms a 200μm thick layer (less in other animals) that lubricates and protects the wall of the organ.[11]
Distinct forms of mucin are produced in different organs: whileMUC2 is prevalent in the intestine,MUC5AC andMUC5B are the main forms found in the humanairway.[12] In the airway, mucus is swept by thecilia of therespiratory epithelium, in a process calledmucociliary clearance, and propelled out of the lungs and into the pharynx, which results in the removal of debris and pathogens from the airway.[13] MUC5AC is overexpressed inhypersensitivity pneumonitis.[13]
Mucins are continuously made and secreted by goblet cells in order to repair and replace the existing mucus layer.[13] Mucins are stored in granules inside the goblet cells before being released to thelumen of the organ.[10] Mucin secretion in the airway may occur via regulated secretion.[14] Secretion may be stimulated by irritants such asdust andsmoke, especially in theairway.[12] Other stimuli aremicrobes such as viruses and bacteria.
Anomalies in the number of goblet cells are associated with changes in the secretion of mucins, which can result in many of the abnormalities seen in asthma patients, such as clogged airways due tomucus hypersecretion, and eventual loss of lung function.[13] Overexpression ofMUC5AC alone does not result in the pathophysiology seen inasthma patients; it is the excessive production along with the speed of secretion that leads to the formation of thick mucus that cannot be removed by cilia or coughing action.[13] This, in addition to airway narrowing leads to the clogging of the airways, which can be detrimental to health if not treated.[13]
There are other cells that secrete mucus (such as thefoveolar cells of thestomach)[15] but these are distinguishedhistologically from goblet cells.
Oral tolerance is the process by which the immune system is prevented from responding to antigen derived from food products, as peptides from food may pass into the bloodstream via the gut, which would in theory lead to an immune response. A paper published inNature in 2012 has shed some light on the process and implicated goblet cells as having a role in the process.[16] It was known thatCD103-expressingdendritic cells of thelamina propria had a role to play in the induction of oral tolerance (potentially by inducing the differentiation ofregulatory T cells), and this paper suggests that the goblet cells act to preferentially deliver antigen to these CD103+ dendritic cells.[16]
The excessive mucus production seen in allergic asthma patients is due togoblet cell metaplasia, thedifferentiation of airway epithelial cells into mucin producing goblet cells.[17] These cells produce the thick mucinsMUC5AC andMUC5B, which clog the airway, leading to the airflow obstruction characteristic ofasthma.[17]
Goblet cell metaplasia in allergic asthma is due to the action of thecytokineIL-13.IL-13 binds to theIL-4Rα receptor and initiates aSTAT6 signalling response.[18] Binding ofIL-13 causesphosphorylation oftyrosine residues at theIL-4Rα.[18] This results in docking ofSTAT6 monomers, which themselves are phosphorylated and then subsequently leave the receptor and congregate form STAT6homodimers in the cytoplasm.[18] These homodimers then enter thenucleus, where they bind to regulatory elements in the DNA, which affects thetranscription of certain genes involved in mucus production.[18]
Induction ofSTAT6 signaling byIL-13 leads to increased of expression of15-lipoxygenase (15-LO-1), which is an enzyme involved in the breakdown of unsaturated fatty acids.[19] 15-lipoxygenase acts by binding tophospholipids and yields hydroperoxy and epoxy metabolites.[19] One such metabolite,15-hydroxyeicosatetranoic acid (15-HETE), is released intracellularly, where it conjugates tophosphatidylethanolamine, a phospholipid component.[19] 15-HETE-PE induces expression of the mucinMUC5AC.[19]
Goblet cell carcinoids are a class of rare tumors that form as a result of an excessive proliferation of both goblet andneuroendocrine cells. The majority of these tumors arise in theappendix and may present symptoms similar to the much more commonacute appendicitis.[20] The main treatment for localized goblet cells tumors isremoval of the appendix, and sometimesremoval of the right hemicolon is also performed.[21] Disseminated tumors may require treatment withchemotherapy in addition to surgery.[20]
_and_foveolar_cells_in_incomplete_Barrett%2527s_esophagus.jpg)
Barrett's esophagus is ametaplasia of the esophagus into intestinal epithelium, characterized by the presence of goblet cells.[22]
Bile acids are a significant factor in the etiology of colorectal cancer.[23] Bile acids induce apoptosis in goblet cells of the colonic mucosa at bile acid concentrations that are comparable to those found in fecal water after high fat-meals.[24][25] An association was observed between resistance to bile acid-induced apoptosis in goblet cells and colon cancer risk.[24][25]
Studies of mice given monoclonalantibodies forIL-13 results in decreased expression of goblet cells inasthma patients.[26] Some treatments that use anti-IL-13 monoclonal antibodies includetralokinumab, andlebrikizumab.[26] These treatments have shown improvements in asthma patients, yet there are still limitations to the use of anti-IL-13 monoclonal antibodies.[26]Dupilumab is a newer drug that targets the shared receptor ofIL-4 andIL-13,IL4Rα.[26] Since IL-4 and IL-13 have interrelated biological activities,Dupilumab is a more effective form of treatment as it targets both interleukins.[26]
The cells were first noted byHenle in 1837 when studying the lining of the small intestine, seen to be mucus producing byLeydig in 1857 (who was examining the epidermis of fish), and were given their name bySchulze in 1867,[27][28] Schulze chose the descriptive name "goblet" because of the shape of the cell, rather than a functional name, as he remained uncertain as to the mucus-producing function of the cell.[28]
In the present day, these cells are used in laboratories to evaluate the intestinal absorption of drug targets with different kits, such as the CacoGoblet.[29]
