Biomedical Engineering Reference
In-Depth Information
12.3.1.1
Goblet Cell
Airway goblet cells are cylindrical-shaped, glandular, simple columnar epithelial
cells. They use both apocrine (decapitation secretion, the apical portion of the
secretory cell of the gland pinching off and entering the lumen) and merocrine
(exocytosis, i.e., membrane-bound vesicle-mediated secretion through the plasma
membrane in the lumen of an epithelial-walled duct) processes for secretion.
They quickly (
100 ms) secrete mucins that covers airway lumen surface with a
protective mucus that is exposed to more or less polluted inhaled air. Numerous
goblet cells (density 3-5
<
10
4
/mm
3
) reside in the respiratory epithelium. Serous
and Clara cells in small airways can transform into goblet cells.
Their apical secretory vesicles are discharged into the airway lumen to form a
mucus layer over the epithelial surface. Peripheral granules in goblet cells produce
the continuous baseline mucus, whereas core granules are secreted in response to
stimuli [
1531
]. Goblet cells contain sialoglycoproteins or a mixture of sialo- and
sulfoglycoproteins.
Secretory cells undergo metaplasia, i.e., a change in phenotype.
4
Interleukin-13
causes goblet cell metaplasia via production and subsequent activation of epidermal
growth factor receptor. Interleukin-13 provokes transcrition of the SCGB1A1 gene
in epithelial non-ciliated cells, more precisely, in non-granulated secretory and
goblet cells [
1533
]. This change in phenotype does not depend upon proliferation;
it is restricted to ScGb1a1
×
+
cells of the tracheobronchial tree, but not ScGb1a1
+
cells of bronchioles [
1534
].
Secretion of oligomeric mucins from airway goblet cells is regulated primarily
by ATP and UTP nucleotides that activate Gq-coupled P2Y
2
receptors, thereby
triggering the PLC-IP
3
-Ca
2
+
and PLC-DAG-PKC intracellular cascades [
1535
].
These pathways coordinate actin cytoskeleton remodeling, thus enabling interaction
of mucin secretory granules with apical membrane exocytic docking sites [
1535
].
Goblet and ciliated cells are indeed characterized by an apical distribution of
β
-actin. In goblet cells, actin forms a cortical sheet between granules
and the apical plasma membrane that ruptures under ATP and UTP stimulation.
Myristoylated alanine-rich C kinase substrate (MARCKS), a PKC-activated actin-
plasma membrane-tethering protein, is phosphorylated upon nucleotide stimulation
and translocates to the core cytosol [
1535
]. In addition, scinderin, or adseverin, a
Ca
2
+
-activated actin filament severing and capping protein in human airway cells,
once it is activated by Ca
2
+
influx, can disassemble actin filaments at sites of
exocytosis and permit mucin secretion. Calcium ion contributes to the regulation
of the final steps of exocytosis in goblet cells, as it interacts with rabphilin homolog,
Uncoordinated-13 homolog Unc13b (or MUnc13),
5
and synaptotagmin.
-and
γ
4
In Greek,
): formation. Metaplasia is the reversible replacement
of a given differentiated cell type by another mature differentiated cell type.
5
The MUNC13 family includes 4 known isoforms (MUnc13-1-MUnc13-4). subtype MUnc13-2
has 2 splice variants. The brain variant bMunc13-2 is similar to MUnc13-3, as it lacks the
τα
) means after, later;
πλασια
Search WWH ::
Custom Search