GSBS Student Publications
GSBS Program
Immunology & Microbiology
Publication Date
2011-10-14
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Article
Disciplines
Biochemistry | Immunology and Infectious Disease
Abstract
Chitin is an abundant polysaccharide found in fungal cell walls, crustacean shells, and insect exoskeletons. The immunological properties of both chitin and its deacetylated derivative chitosan are of relevance because of frequent natural exposure and their use in medical applications. Depending on the preparation studied and the end point measured, these compounds have been reported to induce allergic responses, inflammatory responses, or no response at all. We prepared highly purified chitosan and chitin and examined the capacity of these glycans to stimulate murine macrophages to release the inflammasome-associated cytokine IL-1beta. We found that although chitosan was a potent NLRP3 inflammasome activator, acetylation of the chitosan to chitin resulted in a near total loss of activity. The size of the chitosan particles played an important role, with small particles eliciting the greatest activity. An inverse relationship between size and stimulatory activity was demonstrated using chitosan passed through size exclusion filters as well as with chitosan-coated beads of defined size. Partial digestion of chitosan with pepsin resulted in a larger fraction of small phagocytosable particles and more potent inflammasome activity. Inhibition of phagocytosis with cytochalasin D abolished the IL-1beta stimulatory activity of chitosan, offering an explanation for why the largest particles were nearly devoid of activity. Thus, the deacetylated polysaccharide chitosan potently activates the NLRP3 inflammasome in a phagocytosis-dependent manner. In contrast, chitin is relatively inert.
Keywords
Carbohydrate Chemistry, Chitin, Cytokine Induction, Fungi, Interleukin, Macrophages, Phagocytosis, Chitosan
Rights and Permissions
Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://www.jbc.org/site/misc/Copyright_Permission.xhtml.
DOI of Published Version
10.1074/jbc.M111.274936
Source
J Biol Chem. 2011 Oct 14;286(41):35447-55. doi: 10.1074/jbc.M111.274936. Epub 2011 Aug 23. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
21862582
Repository Citation
Bueter, Chelsea L.; Lee, Chrono K.; Rathinam, Vijay A. K.; Healy, Gloria J.; Taron, Christopher H.; Specht, Charles A.; and Levitz, Stuart M., "Chitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis" (2011). GSBS Student Publications. 2010.
https://escholarship.umassmed.edu/gsbs_sp/2010