Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation
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Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation. / Gorzelanny, Christian; Pöppelmann, Birgit; Pappelbaum, Karin; Moerschbacher, Bruno M; Schneider, Stefan W.
in: BIOMATERIALS, Jahrgang 31, Nr. 33, 11.2010, S. 8556-63.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation
AU - Gorzelanny, Christian
AU - Pöppelmann, Birgit
AU - Pappelbaum, Karin
AU - Moerschbacher, Bruno M
AU - Schneider, Stefan W
N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Cell Line
KW - Chitin
KW - Chitosan
KW - Computational Biology
KW - Hexosaminidases
KW - Humans
KW - Inflammation
KW - Macrophage Activation
KW - Macrophages
KW - Models, Biological
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.biomaterials.2010.07.100
DO - 10.1016/j.biomaterials.2010.07.100
M3 - SCORING: Journal article
C2 - 20797781
VL - 31
SP - 8556
EP - 8563
JO - BIOMATERIALS
JF - BIOMATERIALS
SN - 0142-9612
IS - 33
ER -