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dc.contributor.authorBueter, Chelsea L.
dc.contributor.authorLee, Chrono K.
dc.contributor.authorRathinam, Vijay A. K.
dc.contributor.authorHealy, Gloria J.
dc.contributor.authorTaron, Christopher H.
dc.contributor.authorSpecht, Charles A.
dc.contributor.authorLevitz, Stuart M.
dc.date2022-08-11T08:08:56.000
dc.date.accessioned2022-08-23T16:12:51Z
dc.date.available2022-08-23T16:12:51Z
dc.date.issued2011-10-14
dc.date.submitted2017-09-06
dc.identifier.citation<p>J Biol Chem. 2011 Oct 14;286(41):35447-55. doi: 10.1074/jbc.M111.274936. Epub 2011 Aug 23. <a href="https://doi.org/10.1074/jbc.M111.274936">Link to article on publisher's site</a></p>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M111.274936
dc.identifier.pmid21862582
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33485
dc.description.abstractChitin 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21862582&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsPublisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://www.jbc.org/site/misc/Copyright_Permission.xhtml.
dc.subjectCarbohydrate Chemistry
dc.subjectChitin
dc.subjectCytokine Induction
dc.subjectFungi
dc.subjectInterleukin
dc.subjectMacrophages
dc.subjectPhagocytosis
dc.subjectChitosan
dc.subjectBiochemistry
dc.subjectImmunology and Infectious Disease
dc.titleChitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume286
dc.source.issue41
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3033&amp;context=gsbs_sp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/2010
dc.identifier.contextkey10714504
refterms.dateFOA2022-08-23T16:12:51Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathgsbs_sp/2010
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages35447-55
dc.contributor.studentChelsea L. Bueter


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