Chitotriosidase: the yin and yang

Abstract

The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering from Gaucher's disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation might have different functional meanings in various diseases.

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

“…[7][8][9][10] Little is known regarding the physiological function of CHIT-1, although its phagocyte-specific expression points to a role of the enzyme in innate immunity. [11][12] CHIT-1 mRNA expression is upregulated after stimulation by tumor necrosis factor alpha (TNF-a), interferon gamma (IFN-g), prolactin and lipopolysaccharide (LPS). [13][14][15] In vitro studies using recombinant human CHIT-1 have demonstrated that CHIT-1 lyses the hyphal tip of Mucor rouxii and inhibits the growth of hyphae of Candida albicans.…”

A Rare Cause of Elevated Chitotriosidase Activity: Glycogen Storage Disease Type IV

“…Fungal and granulomatous infections like tuberculosis and leishmaniasis, malaria, bthalassemia, sarcoidosis, Wegener's granulomatosis, cerebral adrenoleukodystrophy, atherosclerosis, nonalcoholic liver disease, diabetes mellitus, multiple sclerosis, Alagille syndrome, GSD type I and IV, lung and prostate cancer are the diseases in the literature that have been related with elevated plasma chitotriosidase activity and inflammation (Hollak et al 1994;Altarescu et al 2002;Michelakakis et al 2004;Malaguarnera 2006;Orchard et al 2011;Kanneganti et al 2012;Tumer et al 2013). …”

“…In two chronic liver diseases, nonalcoholic steatohepatitis and GSD type I, lipid accumulation, and peroxidation in hepatocytes trigger activation of resident macrophages of the liver (Kupffer cells). As a consequence, this activation induces proinflammatory cytokines and results in secretion of chitotriosidase (Malaguarnera 2006;Tumer et al 2013). Besides this, Kupffer cells also activate hepatic stellate cells that synthesize several extracellular matrix components and also induce hepatic fibrosis and ultimately liver cirrhosis.…”

Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties

“…The screen revealed several potential binding partners for YKL-39 ( Figure 1A). A common characteristic of these glycan ligands was the presence of β (1,4) glycosidic bonds, and the strongest binders were the chitooligosaccharides (GlcNAc) 5 and (GlcNAc) 6 . To quantify the strength of this interaction, intrinsic tryptophan fluorescence was used, exploiting the presence of several conserved tryptophan residues ( Figure 1B), which have been shown to play a role in substrate binding by family 18 chitinase [31,43,44].…”

“…The C-terminal domain of the 39 kDa isoform has been shown to be involved in the binding of chitin [3], whereas the 50 kDa form is secreted from macrophages and the truncated form is not. Rather, it is routed to the lysosomes and can be used as a marker for measuring the progression of Gaucher's disease [4][5][6]. AMCase has a similar domain structure, but a distinct expression pattern, being expressed in the gastrointestinal tract and lung by tissue macrophages and endothelial cells [7,8].…”