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 secretions, when under stress.
The term ''
goblet'' 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, 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, co ...
.
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
organ
Organ may refer to:
Biology
* Organ (biology), a part of an organism
Musical instruments
* Organ (music), a family of keyboard musical instruments characterized by sustained tone
** Electronic organ, an electronic keyboard instrument
** Hammond ...
s, such as the
intestinal 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 t ...
,
bronchi, and larger
bronchioles in the respiratory tract,
small intestines, the
large intestine, 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 epithel ...
in the upper
eyelid. 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 epithel ...
goblet cells are a source of mucin in
tears and they also secrete different types of mucins onto the
ocular
Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
surface. In the
lacrimal glands, 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 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 i ...
, 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 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 ...
. 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 v ...
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 o ...
-rich proteins are washed out in the
preparation 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
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
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 membranes where they are found. Goblet cells accomplish this by secreting
mucins, 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 glyco ...
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 o ...
s. The gel-like properties of mucins are given by its
glycans (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 Uni ...
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 t ...
.
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 proje ...
of the
respiratory epithelium, in a process called
mucociliary clearance, 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 dermati ...
.
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, 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 t ...
.
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, co ...
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) but these are distinguished
histologically from goblet cells.
Role in oral tolerance
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 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
Integrin, alpha E (ITGAE) also known as CD103 (cluster of differentiation 103) is an integrin protein that in human is encoded by the ''ITGAE'' gene. CD103 binds integrin beta 7 (β7– ITGB7) to form the complete heterodimeric integrin molecu ...
-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. Th ...
s of the
lamina propria
The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenit ...
had a role to play in the induction of oral tolerance (potentially by inducing the differentiation of
regulatory T cells), 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, co ...
.
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 au ...
IL-13.
IL-13 binds to the
IL-4Rα receptor and initiates a
STAT6 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, wh ...
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 G ...
residues at the
IL-4Rα.
This results in docking of
STAT6 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 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 typ ...
s and yields hydroperoxy and epoxy metabolites.
One such metabolite,
15-hydroxyeicosatetranoic acid (15-HETE), is released intracellularly, where it conjugates to
phosphatidylethanolamine, 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 appendicit ...
s are a class of rare tumors that form as a result of an excessive proliferation of both goblet and
neuroendocrine cells. 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 (pu ...
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. Chemother ...
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 cells ...
is a
metaplasia of the esophagus into intestinal epithelium, characterized by the presence of goblet cells.
Treatments
Monoclonal antibodies
Studies of mice given monoclonal
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
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, co ...
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 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 is a more effective form of treatment as it targets both interleukins.
History
The cells were first noted by
Henle Henle can refer to:
*Friedrich Gustav Jakob Henle, a German physician, pathologist and anatomist (1809–1885)
** Loop of Henle
In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni ...
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
Schulze is a German surname, from the medieval office of Schulze, or village official. Notable people with the surname include:
* Andrew Schulze (1896–1982), clergyman and civil rights activist
* William August Schulze, rocket scientist recru ...
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
* Corti ...
References
External links
Goblet Cells at cvmbs.colostate.edu
{{Authority control
Mucus secreting cells
Epithelial cells
Human cells