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

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

Authors :
Lucile E Wrenshall
Suzanne E Clabaugh
David R Cool
Prakash Arumugam
William C Grunwald
Deandra R Smith
Gino C Liu
John D Miller
Source :
PLoS ONE, Vol 9, Iss 7, p e102191 (2014)
Publication Year :
2014
Publisher :
Public Library of Science (PLoS), 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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
9
Issue :
7
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.bad86626563441da1df31c3ec58e59c
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0102191