Document Type
Article
Publication Date
7-14-2014
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.
Repository 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.
https://corescholar.libraries.wright.edu/surg/713
DOI
10.1371/journal.pone.0102191
Comments
© 2014 Wrenshall, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.