Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues

  • PLoS One. 2014 Jul 14;9(7):e102191. doi: 10.1371/journal.pone.0102191.
Lucile E Wrenshall  1 ,  Suzanne E Clabaugh  1 ,  David R Cool  2 ,  Prakash Arumugam  1 ,  William C Grunwald  2 ,  Deandra R Smith  3 ,  Gino C Liu  1 ,  John D Miller  1
Affiliations
  • 1. Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine Wright State University, Dayton, Ohio, United States of America.
  • 2. Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, United States of America.
  • 3. Eppley Institute for Cancer Research, University of Nebraska at Omaha, Omaha, Nebraska, United States of America.
PMID: 25019288 DOI: 10.1371/journal.pone.0102191
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.

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