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Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation

Paper ID Volume ID Publish Year Pages File Format Full-Text
8839 608 2010 8 PDF Available
Title
Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation
Abstract

Chitin a biopolymer composed of N-acetyl-d-glucosamine (GlcNAc) residues is a structural component in human pathogens such as nematodes and fungi. Deacetylation of chitin generates chitosan which has been recently found in the cell wall of Cryptococcus neoformans a human pathogenic fungi causing life-threatening meningoencephalitis. While chitin and chitosan are currently studied as compounds of medical devices such as wound dressings or nanoparticles, its immunostimulatory potential and its metabolic fate in humans remains unclear. To gain more fundamental insights on the immunological properties of chitin and chitosan in humans we studied their degradation by chitotriosidase (ChT) and their inflammatory properties on human macrophages. Our data show that chitinhexamer is not able to increase the expression of inflammatory cytokines significantly. However, we measured an induction of ChT secretion upon chitinhexamer treatment. By analysis of human ChT-mediated cleavage of chitosan we could demonstrate a special mechanism of substrate cleavage, defined as processivity. Processivity enables the rapid production of small and diffusible chitin and chitosan fragments. In comparison to large chitosan polymers these ChT-produced small chitin/chitosan oligomers exhibit strongest macrophage activating properties reflected by an enhanced ChT secretion. Here we show that recognition of chitin and chitosan by human macrophages is triggered by the enzyme ChT due to the production of chitin and chitosan oligomers which in turn stimulates further ChT secretion and consequently oligomers production. Finally, we demonstrate that despite the high cooperativity of chitosan and chitin clearance by ChT seems very specific as no inflammatory response could be detected.

Keywords
Chitin/Chitosan; Mammalian chitinase; Innate immunity; Biocompatibility; Inflammation
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Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 33, November 2010, Pages 8556–8563
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us