Role of Chitotriosidase (Chitinase 1) Under Normal and Disease Conditions

Abstract

Mammalian chitinases belong to the glycosyl hydrolase 18 family based on structural homology and the family includes a large number of bacterial and eukaryotic chitinases. Among the mammalian chitinases, chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are capable of hydrolyzing the β-(1, 4)-linkage between the adjacent N-acetyl glucosamine residues of chitin. CHIT1 is one of the most abundantly secreted proteins, being mainly produced by activated macrophages and epithelial cells. CHIT1 plays a pivotal role in the context of infectious disease including malaria and fungi infections as a host defense towards chitin in pathogen's cell structure and as a diagnostic marker of disease. In contrast, CHI1 released by activated Kupffer cells in liver could induce hepatic fibrosis and cirrhosis. Increased serum levels of CHIT1 were observed in patients with many disorders, including Gaucher's disease, bronchial asthma, and atherosclerosis. Therefore, CHIT1 seems to have dual (regulatory and pathogenic) roles depending on the disease and producing cell types during the inflammatory conditions.

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

“…Besides this, chitotriosidase activity is also known to be directly associated with acute or chronic inflammatory conditions (Kanneganti et al 2012). In Gaucher disease, storage of glucocerebroside in macrophages causes proinflammatory activation and finally elevation of chitotriosidase.…”

“…Similar mechanism is also observed in NPD. Massive increased activity of chitotriosidase is a hallmark of Gaucher disease (10-1,000-fold), while other conditions have less elevated levels (Sheth et al 2010;Kanneganti et al 2012). Limited reports are available about chitotriosidase levels in other LSD (Michelakakis et al 2004;Sheth et al 2010).…”

“…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). …”

“…Elevated chitotriosidase activities have also been reported in various diseases related with macrophage activation (Michelakakis et al 2004;Kanneganti et al 2012;Tumer et al 2013).…”

“…However, in 1994, Hollak et al reported the first discovered mammalian chitinase -chitotriosidase -that was found to be significantly elevated in the serum of patients with Gaucher disease (Hollak et al 1994;Gorzelanny et al 2010). Chitotriosidase is mainly produced, stored, and secreted by activated macrophages and neutrophils (Kanneganti et al 2012). Primary indication for studying chitotriosidase activity is screening for lysosomal storage diseases (LSD), especially Gaucher and Niemann-Pick disease (NPD) A/B (Sheth et al 2010).…”