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https://doi.org/10.1371/journal.pone.0102191
Title: | Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues | Authors: | Wrenshall L.E. Clabaugh S.E. Cool D.R. Arumugam P. Grunwald W.C. Smith D.R. Liu G.C. Miller J.D. |
Keywords: | heparanase interleukin 2 interleukin 2 receptor alpha interleukin 2 receptor gamma protein glutamine gamma glutamyltransferase interleukin 2 animal cell animal experiment animal model animal tissue apoptosis article cell death cell killing controlled study cytotoxicity epithelium cell human human cell in vivo study lymphocyte membrane permeability mouse nonhuman protein expression protein function vascular smooth muscle animal Bagg albino mouse cell death cell membrane permeability chemistry dimerization drug effects mass spectrometry metabolism smooth muscle fiber Western blotting Animals Blotting, Western Cell Death Cell Membrane Permeability Dimerization Epithelial Cells Interleukin-2 Lymphocytes Mice Mice, Inbred BALB C Myocytes, Smooth Muscle Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization |
Issue Date: | 2014 | Citation: | Wrenshall L.E., Clabaugh S.E., Cool D.R., Arumugam P., Grunwald W.C., Smith D.R., Liu G.C., Miller J.D. (2014). Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues. PLoS ONE 9 (7) : e102191. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0102191 | Rights: | Attribution 4.0 International | Abstract: | Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include "traditional" IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems. © 2014 Wrenshall et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161399 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0102191 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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