Goblet cells are simple columnar epithelial cells that secrete gel-forming , like mucin 2 in the lower gastrointestinal tract, and mucin 5AC in the respiratory tract.
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 to give an increased surface area for secretion.]
Goblet cells are typically found in the respiratory, reproductive and lower gastrointestinal tracts and are surrounded by other columnar cells.[ Metaplasia 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.]
Structure
Goblet cells are found scattered among the
epithelium lining of organs, such as the intestinal and respiratory tracts.
They are found inside the
trachea,
bronchi, and larger
bronchioles in the respiratory tract,
small intestines, the
large intestine, and
conjunctiva in the upper
eyelid. In the
conjunctiva goblet cells are a source of mucin in
tears and they also secrete different types of mucins onto the
ocular surface. In the
, mucus is
biosynthesis by
Acinus instead.
Microanatomy
Goblet cells are simple columnar epithelial cells, having a height of four times that of their width. The
cytoplasm 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, which lies between the granules and the
cell nucleus. This gives the basal part of the cell a
basophilic staining because of
within the nucleus and rough endoplasmic reticulum staining with
hematoxylin. Mucin within the granules stains pale in routine
histology sections, primarily because these
carbohydrate-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.
from the human intestine with goblet cells visible]]
]]
]]
Function
The main role of goblet cells is to secrete
mucus in order to protect the
where they are found. Goblet cells accomplish this by secreting
, large
formed mostly by
. The gel-like properties of mucins are given by its
(bound carbohydrates) attracting relatively large quantities of water.
On the inner surface of the human intestine, it forms a 200
micrometre 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.[
]
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.][ 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 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 of the stomach)[ - Digestive System: Alimentary Canal: fundic stomach, gastric glands, lumen"] but these are distinguished histology 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-expressing
of the
lamina propria 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 Metaplasia of airway epithelial cells into mucin producing goblet cells.[
]
Goblet cell metaplasia in allergic asthma is due to the action of the cytokine IL-13. IL-13 binds to the IL-4Rα receptor and initiates a STAT6 signalling response.[ This results in docking of STAT6 monomers, which themselves are phosphorylated and then subsequently leave the receptor and congregate form STAT6 Protein dimer in the cytoplasm.][ These homodimers then enter the Cell nucleus, 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 (15-LO-1), which is an enzyme involved in the breakdown of unsaturated fatty acids.[ 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 carcinoids 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 and may present symptoms similar to the much more common acute appendicitis.[
]
Metaplasia
Barrett's esophagus is a metaplasia of the esophagus into intestinal epithelium, characterized by the presence of goblet cells.
Colonic mucosa
/ref>[
]
Treatments
Monoclonal antibodies
Studies of mice given monoclonal Antibody for IL-13 results in decreased expression of goblet cells in asthma patients.[ 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 in 1837 when studying the lining of the small intestine, seen to be mucus producing by Franz Leydig in 1857 (who was examining the epidermis of fish), and were given their name by Schulze in 1867,[
]
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.
See also
-
List of human cell types derived from the germ layers
-
List of distinct cell types in the adult human body
External links
