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Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues.
- Source :
-
PloS one [PLoS One] 2014 Jul 14; Vol. 9 (7), pp. e102191. Date of Electronic Publication: 2014 Jul 14 (Print Publication: 2014). - Publication Year :
- 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 :
- Animals
Blotting, Western
Dimerization
Epithelial Cells metabolism
Lymphocytes metabolism
Mice
Mice, Inbred BALB C
Myocytes, Smooth Muscle metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Cell Death drug effects
Cell Membrane Permeability drug effects
Epithelial Cells drug effects
Interleukin-2 chemistry
Interleukin-2 toxicity
Lymphocytes drug effects
Myocytes, Smooth Muscle drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25019288
- Full Text :
- https://doi.org/10.1371/journal.pone.0102191