;HSGAGs: Endogenous heparin is localized and stored in secretory granules of
mast cells.
Histamine that is present within the granules is protonated (H2A2+) at pH within granules (5.2–6.0), thus it is believed that heparin, which is highly negatively charged, functions to electrostatically retain and store histamine. In the clinic, heparin is administered as an anticoagulant and is also the first line choice for thromboembolic diseases. Heparan sulfate (HS) has numerous biological activities and functions, including cell adhesion, regulation of cell growth and proliferation, developmental processes, cell surface binding of lipoprotein lipase and other proteins, angiogenesis, viral invasion, and tumor metastasis. while interactions with hepatic growth factor/scatter factor (HGF/SF) activate the HGF/SF signaling pathway (
c-Met) through its receptor. CSGAGs are important in providing support and adhesiveness in bone, skin, and cartilage. Other biological functions for which CSGAGs are known to play critical functions in include inhibition of axonal growth and regeneration in CNS development, roles in brain development, neuritogenic activity, and pathogen infection. ;Keratan sulfates:One of the main functions of the third class of GAGs, keratan sulfates, is the maintenance of tissue hydration. In disease states such as
macular corneal dystrophy, in which GAGs levels such as KS are altered, loss of hydration within the corneal stroma is believed to be the cause of corneal haze, thus supporting the long-held hypothesis that corneal transparency is dependent on proper levels of keratan sulfate. Keratan sulfate GAGs are found in many other tissues besides the cornea, where they are known to regulate
macrophage adhesion, form barriers to
neurite growth, regulate
embryo implantation in the endometrial uterine lining during menstrual cycles, and affect the motility of corneal endothelial cells. The
viscoelasticity of hyaluronic acid makes it ideal for lubricating joints and surfaces that move along each other, such as cartilage. A solution of hyaluronic acid under low
shear stress has a much higher viscosity than while under high shear stress.
Hyaluronidase, an enzyme produced by white blood cells, sperms cells, and some bacteria, breaks apart the hyaluronic acid, causing the solution to become more liquid. :
In vivo, hyaluronic acid forms randomly kinked coils that entangle to form a hyaluronan network, slowing diffusion and forming a diffusion barrier that regulates transport of substances between cells. For example, hyaluronan helps partition plasma proteins between vascular and extravascular spaces, which affects solubility of macromolecules in the interstitium, changes chemical equilibria, and stabilizes the structure of collagen fibers. :Other functions include matrix interactions with hyaluronan binding proteins such as hyaluronectin, glial hyaluronan binding protein, brain enriched hyaluronan binding protein,
collagen VI,
TSG-6, and
inter-alpha-trypsin inhibitor. Cell surface interactions involving hyaluronan are its well-known coupling with
CD44, which may be related to tumor progression, and also with RHAMM (
Hyaluronan-mediated motility receptor), which has been implicated in developmental processes, tumor metastasis, and pathological reparative processes. :Fibroblasts, mesothelial cells, and certain types of stem cells surround themselves in a
pericellular "coat", part of which is constructed from hyaluronan, in order to shield themselves from bacteria, red blood cells, or other matrix molecules. For example, in regard to stem cells, hyaluronan, along with chondroitin sulfate, helps to form the
stem cell niche. Stem cells are protected from the effects of growth factors by a shield of hyaluronan and minimally sulfated chondroitin sulfate. During progenitor division, the daughter cell moves outside of this pericellular shield where it can then be influenced by growth factors to differentiate even further. ==Classification==