1. Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues
- Author
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William C. Grunwald Jr., Suzanne E. Clabaugh, Gino C. Liu, Lucile E. Wrenshall, John D. Miller, Prakash Arumugam, Deandra R. Smith, and David R. Cool
- Subjects
Cell Membrane Permeability ,Physiology ,medicine.medical_treatment ,Receptor expression ,lcsh:Medicine ,Biochemistry ,Mice ,Animal Cells ,Immune Physiology ,Molecular Cell Biology ,Morphogenesis ,Cytotoxic T cell ,Cell Cycle and Cell Division ,Lymphocytes ,lcsh:Science ,Mice, Inbred BALB C ,Multidisciplinary ,Cell Death ,Animal Models ,3. Good health ,Cell biology ,Cytokine ,Cell Processes ,Cytokines ,Anatomy ,Cellular Types ,Dimerization ,Research Article ,medicine.drug ,Interleukin 2 ,Cell Physiology ,Programmed cell death ,Cell type ,Membrane permeability ,Immune Cells ,Immunology ,Blotting, Western ,Myocytes, Smooth Muscle ,Mouse Models ,Biology ,Research and Analysis Methods ,Model Organisms ,medicine ,Animals ,Heparanase ,Molecular Biology Techniques ,Sequencing Techniques ,Molecular Biology ,Cytokinesis ,lcsh:R ,Immunity ,Biology and Life Sciences ,Proteins ,Epithelial Cells ,Cell Biology ,Molecular Development ,Immune System ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Cardiovascular Anatomy ,Interleukin-2 ,lcsh:Q ,Developmental Biology - 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.
- Published
- 2014