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Goblet cells are simple columnar epithelial cells that secrete gel-forming
mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in m ...
s, like
mucin 5AC Mucin-5AC (MUC-5AC) is a protein that in humans is encoded by the ''MUC5AC'' gene. MUC-5AC is a large gel-forming glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains ...
. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use
apocrine Apocrine () glands are a type of exocrine gland, which are themselves a type of gland, i.e. a group of cells specialized for the release of secretions. Exocrine glands secrete by one of three means: holocrine, merocrine and apocrine. In apocrine ...
methods, budding off their secretions, when under stress. The term ''
goblet A chalice (from Latin 'mug', borrowed from Ancient Greek () 'cup') or goblet is a footed cup intended to hold a drink. In religious practice, a chalice is often used for drinking during a ceremony or may carry a certain symbolic meaning. R ...
'' 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. The apical plasma membrane projects short
microvilli Microvilli (singular: 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, ...
to give an increased surface area for secretion. Goblet cells are typically found in the respiratory, reproductive and gastrointestinal tracts and are surrounded by other columnar cells. Biased differentiation of airway basal cells in the
respiratory epithelium Respiratory epithelium, or airway epithelium, is a type of ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways. It is not present in the vocal cords o ...
, into goblet cells plays a key role in the excessive mucus production, known as mucus hypersecretion seen in many respiratory diseases, including chronic bronchitis, and
asthma Asthma is a 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 wheezing, c ...
.


Structure

Goblet cells are found scattered among the
epithelial 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 intercellu ...
lining of organs, such as the
intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...
and
respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to ...
s. They are found inside the
trachea The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends from th ...
,
bronchi A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronch ...
, and larger bronchioles in the respiratory tract, small intestines, the
large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...
, and
conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epitheli ...
in the upper
eyelid An eyelid is a thin fold of skin that covers and protects an eye. The levator palpebrae superioris muscle retracts the eyelid, exposing the cornea to the outside, giving vision. This can be either voluntarily or involuntarily. The human eyel ...
. In the
conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epitheli ...
goblet cells are a source of mucin in
tears Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...
and they also secrete different types of mucins onto the ocular surface. In the
lacrimal gland The lacrimal glands are paired exocrine glands, one for each eye, found in most terrestrial vertebrates and some marine mammals, that secrete the aqueous layer of the tear film. In humans, they are situated in the upper lateral region of each o ...
s, mucus is synthesized by acinar cells instead.


Microanatomy

Goblet cells are simple columnar epithelial cells, having a height of four times that of their width. The
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
of goblet cells tends to be displaced toward the basal end of the cell body by the large
mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in m ...
granules, which accumulate near the apical surface of the cell along 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 ...
, which lies between the granules and the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...
. This gives the basal part of the cell a basophilic staining because of
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
s within the nucleus and
rough 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 ( ...
staining with
hematoxylin Haematoxylin or hematoxylin (), also called natural black 1 or C.I. 75290, is a compound extracted from heartwood of the logwood tree ('' Haematoxylum campechianum'') with a chemical formula of . This naturally derived dye has been used as a ...
. Mucin within the granules stains pale in routine
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vi ...
sections, primarily because these
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ...
-rich proteins are washed out in the
preparation Preparation may refer to: * Preparation (dental), the method by which a tooth is prepared when removing decay and designing a form that will provide adequate retention for a dental restoration * Preparation (music), treatment of dissonance in tona ...
of microscopy samples. However, they stain easily with the PAS staining method, which colours them magenta. In mucicarmine 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. File:Gray1062.png, An intestinal gland from the human intestine with goblet cells visible File:Gobletcell.jpg, Goblet cell in
ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
File:MultiPhotonExcitation-Fig10-doi10.1186slash1475-925X-5-36.JPEG, Section of mouse intestine, mucus of goblet cells in blue File:Goblet cells.jpg, Goblet cells in
large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...


Function

The main role of goblet cells is to secrete
mucus 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 ...
in order to protect the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
s where they are found. Goblet cells accomplish this by secreting
mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in m ...
s, large
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...
s formed mostly by
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ...
s. The gel-like properties of mucins are given by its
glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate ...
s (bound carbohydrates) attracting relatively large quantities of water. On the inner surface of the human intestine, it forms a 200
µm The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American spelling), also commonly known as a micron, is a unit of length in the International System of Unit ...
thick layer (less in other animals) that lubricates and protects the wall of the organ. Distinct forms of mucin are produced in different organs: while MUC2 is prevalent in the intestine, MUC5AC and MUC5B are the main forms found in the human
airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to ...
. In the airway, mucus is swept by the
cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
of the
respiratory epithelium Respiratory epithelium, or airway epithelium, is a type of ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways. It is not present in the vocal cords o ...
, in a process called
mucociliary clearance Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator, describes the self-clearing mechanism of the airways in the respiratory system. It is one of the two protective processes for the lungs in removing inhaled parti ...
, and propelled out of the lungs and into the pharynx, which results in the removal of debris and pathogens from the airway. MUC5AC is overexpressed in
allergic lung inflammation Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
. Mucins are continuously made and secreted by goblet cells in order to repair and replace the existing mucus layer. Mucins are stored in granules inside the goblet cells before being released to the lumen of the organ. Mucin secretion in the airway may occur via regulated secretion. Secretion may be stimulated by irritants such as
dust Dust is made of fine particles of solid matter. On Earth, it generally consists of particles in the atmosphere that come from various sources such as soil lifted by wind (an aeolian process), volcanic eruptions, and pollution. Dust in ...
and
smoke Smoke is a suspension of airborne particulates and gases emitted when a material undergoes combustion or pyrolysis, together with the quantity of air that is entrainment (engineering), entrained or otherwise mixed into the mass. It is commo ...
, especially in the
airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to ...
. Other stimuli are microbes 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 to mucus hypersecretion, and eventual loss of lung function. Overexpression of MUC5AC alone does not result in the pathophysiology seen in
asthma Asthma is a 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 wheezing, c ...
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. This, in addition to airway narrowing leads to the clogging of the airways, which can be detrimental to health if not treated.   There are other cells that secrete mucus (such as the foveolar cells of the
stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
) but these are distinguished histologically from goblet cells.


Role in oral tolerance

Oral tolerance Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that would otherwise have the capacity to elicit an immune response in a given organism. It is induced by ...
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 in ''Nature'' in 2012 has shed some light on the process and implicated goblet cells as having a role in the process. It was known that CD103-expressing
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s of the lamina propria had a role to play in the induction of oral tolerance (potentially by inducing the differentiation of
regulatory T cells The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosu ...
), and this paper suggests that the goblet cells act to preferentially deliver antigen to these CD103+ dendritic cells.


Clinical significance


Allergic asthma

The excessive mucus production seen in allergic asthma patients is due to goblet cell metaplasia, the differentiation of airway epithelial cells into mucin producing goblet cells. These cells produce the thick mucins MUC5AC and MUC5B, which clog the airway, leading to the airflow obstruction characteristic of
asthma Asthma is a 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 wheezing, c ...
. Goblet cell metaplasia in allergic asthma is due to the action of the
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
IL-13. IL-13 binds to the IL-4Rα receptor and initiates a
STAT6 Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins. The proteins of STAT family transmit signals from a receptor co ...
signalling response. Binding of IL-13 causes
phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...
of
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
residues at the IL-4Rα. This results in docking of
STAT6 Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins. The proteins of STAT family transmit signals from a receptor co ...
monomers, which themselves are phosphorylated and then subsequently leave the receptor and congregate form STAT6 homodimers in the cytoplasm. These homodimers then enter the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...
, where they bind to regulatory elements in the DNA, which affects the transcription of certain genes involved in mucus production. Induction of
STAT6 Signal transducer and activator of transcription 6 (STAT6) is a transcription factor that belongs to the Signal Transducer and Activator of Transcription (STAT) family of proteins. The proteins of STAT family transmit signals from a receptor co ...
signaling by IL-13 leads to increased of expression of
15-lipoxygenase ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically importa ...
(15-LO-1), which is an enzyme involved in the breakdown of unsaturated fatty acids. 15-lipoxygenase acts by binding to
phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids ty ...
s and yields hydroperoxy and epoxy metabolites. One such metabolite, 15-hydroxyeicosatetranoic acid (15-HETE), is released intracellularly, where it conjugates to
phosphatidylethanolamine Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate- ethanolamine to diglycerides, releasing cytidine monophosphate. ''S''-Adenosyl methionine ...
, a phospholipid component. 15-HETE-PE induces expression of the mucin MUC5AC.


Goblet cell carcinoids

Goblet cell carcinoid The goblet cell carcinoid (GCC) is a rare biphasic gastrointestinal tract tumour that consists of a neuroendocrine component and a conventional carcinoma, histologically arising from Paneth cells. Sign and symptoms GCCs may present as appendicitis ...
s are a class of rare tumors that form as a result of an excessive proliferation of both goblet and
neuroendocrine cell Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they br ...
s. The majority of these tumors arise in the
appendix Appendix, or its plural form appendices, may refer to: __NOTOC__ In documents * Addendum, an addition made to a document by its author after its initial printing or publication * Bibliography, a systematic list of books and other works * Index (pub ...
and may present symptoms similar to the much more common acute appendicitis. The main treatment for localized goblet cells tumors is removal of the appendix, and sometimes removal of the right hemicolon is also performed. Disseminated tumors may require treatment with
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
in addition to surgery.


Metaplasia

Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cel ...
is a
metaplasia Metaplasia ( gr, "change in form") is the transformation of one differentiated cell type to another differentiated cell type. The change from one type of cell to another may be part of a normal maturation process, or caused by some sort of abn ...
of the esophagus into intestinal epithelium, characterized by the presence of goblet cells.


Treatments


Monoclonal antibodies

Studies of mice given monoclonal antibodies for IL-13 results in decreased expression of goblet cells in
asthma Asthma is a 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 wheezing, c ...
patients. Some treatments that use anti-IL-13 monoclonal antibodies include tralokinumab, and lebrikizumab. These treatments have shown improvements in asthma patients, yet there are still limitations to the use of anti-IL-13 monoclonal antibodies.
Dupilumab Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as eczema (atopic dermatitis), asthma and nasal polyps which result in chronic sinusitis. I ...
is a newer drug that targets the shared receptor of IL-4 and IL-13, IL4Rα. Since IL-4 and IL-13 have interrelated biological activities,
Dupilumab Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as eczema (atopic dermatitis), asthma and nasal polyps which result in chronic sinusitis. I ...
is a more effective form of treatment as it targets both interleukins.


History

The cells were first noted by Henle in 1837 when studying the lining of the small intestine, seen to be mucus producing by Leydig in 1857 (who was examining the epidermis of fish), and were given their name by Schulze in 1867, 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 mucous-producing function of the cell. Nowadays these cells are used in the laboratories to evaluate the intestinal absorption of drug targets with different kits, such as the CacoGoblet.


See also

*
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 * Corticot ...


References


External links


Goblet Cells at cvmbs.colostate.edu
{{Authority control Mucus secreting cells Epithelial cells Human cells