Chitins and chitinase activity in airway diseases

Abstract

Chitin, one of the most abundant biopolymers on Earth, is bound and degraded by chitinases, specialized enzymes that are similarly widespread in nature. Chitin catabolism affects global carbon and nitrogen cycles through a host of diverse biological processes, but recent work has focused attention on systems of chitin recognition and degradation conserved in mammals, connecting an ancient pathway of polysaccharide processing to human diseases influenced by persistent immune triggering. Here we review current advances in our understanding of how chitin-chitinase interactions affect mucosal immune feedback mechanisms essential to maintaining homeostasis and organ health.

Keywords: Acidic mammalian chitinase; age-related disease; chitin; chitinase; chitotriosidase; epithelium; fibrosis; innate lymphoid cell; interleukins; interstitial lung disease; polysaccharide; pulmonary fibrosis.

Figure 1.. Organization of natural chitin structures.

Chitin (exemplified by crustacean exoskeleton; A) is layered in repeating planar arrays comprised of mineralized chitin-protein fibers (B-E). Within these fibers, extensive hydrogen bonding organizes linear polymeric N-acetyl-glucosamine chains into nanofibrils (F-H), which can be internally cleaved by endochitinases, or at free non-reducing ends by exochitinases (G; arrows). Illustration based on Nikolov et al., Adv. Mater. 22:519–26; 2010.

Figure 2.. Airway chitinase activity maintains lung health and homeostasis.

In normal healthy airways (left panel), acidic mammalian chitinase (AMCase; arrows) degrades environmentally-derived chitin polymers. In the absence of AMCase (right panel), chitin polymers accumulate in the airways, leading to epithelial stress, chronic activation of resident lymphoid cells, inflammatory cell and cytokine production and age-related fibrosis.