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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Immunol 2014 ; 192 (12): 5943-51 Nephropedia Template TP
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Spectrum and Mechanisms of Inflammasome Activation by Chitosan #MMPMID24829412
Bueter CL; Lee CK; Wang JP; Ostroff GR; Specht CA; Levitz SM
J Immunol 2014[Jun]; 192 (12): 5943-51 PMID24829412show ga
Chitosan, the deacetylated derivative of chitin, can be found in the cell wall of some fungi and is utilized in translational applications. We have shown that highly purified preparations of chitosan, but not chitin, activate the NLRP3 inflammasome in primed mouse bone marrow-derived macrophages (BMM?), inducing a robust IL-1? response. Here, we further define specific cell types that are activated and delineate mechanisms of activation. BMM? differentiated to promote a classically activated (M1) phenotype released more IL-1? in response to chitosan than intermediate or alternatively activated macrophages (M2). Chitosan but not chitin induced a robust IL-1? response in mouse DCs, peritoneal macrophages, and human PBMCs. Three mechanisms for NLRP3 inflammasome activation may contribute: K+ efflux, reactive oxygen species (ROS), and lysosomal destabilization. The contributions of these mechanisms were tested using a K+ efflux inhibitor, high extracellular potassium, a mitochondrial ROS inhibitor, lysosomal acidification inhibitors, and a cathepsin B inhibitor. These studies revealed that each of these pathways participated in optimal NLRP3 inflammasome activation by chitosan. Finally, neither chitosan nor chitin stimulated significant release from unprimed BMM? of any of 22 cytokines and chemokines assayed. In conclusion, 1) chitosan, but not chitin, stimulates IL-1? release from multiple murine and human cell types; 2) multiple non-redundant mechanisms appear to participate in inflammasome activation by chitosan; and 3) chitin and chitosan are relatively weak stimulators of inflammatory mediators from unprimed BMM?. These data have implications for understanding the nature of the immune response to microbes and biomaterials that contain chitin and chitosan.