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The CCL3/macrophage inflammatory protein-1alpha-binding protein evasin-1 protects from graft-versus-host disease but does not modify graft-versus-leukemia in mice.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Mar 01; Vol. 184 (5), pp. 2646-54. Date of Electronic Publication: 2010 Jan 25. - Publication Year :
- 2010
-
Abstract
- CCL3 is a protein of the CC chemokine family known to be important for T cell recruitment in inflammatory diseases. The aim of the current study was to evaluate the effects and putative mechanism of action of evasin-1, a novel CCL3-binding protein, in the pathogenesis of acute graft-versus-host disease (GVHD). GVHD was induced by the transplantation of splenocytes from C57BL/6J to B6D2F1 mice. Treatment of recipient mice with evasin-1 prevented mortality associated with GVHD. This was correlated with reduced weight loss and clinical disease severity. Analysis of the small intestine showed that evasin-1 treatment reduced the histopathological score and decreased levels of IFN-gamma and CCL5. Mechanistically, evasin-1 treatment reduced the number of CD4(+) and CD8(+) T cells infiltrating the small intestine, as assessed by immunohistochemistry, and the adhesion of leukocytes to intestinal venules of recipient mice, as assessed by intravital microscopy. Evasin-1 was also able to decrease liver damage, as seen by reduction of inflammatory infiltrate and IFN-gamma levels. Treatment with evasin-1 did not interfere with graft-versus-leukemia. Altogether, our studies demonstrate that CCL3 plays a major role in mediating GVHD, but not graft-versus-leukemia in mice and suggest that blockade of CCL3 with evasin-1 has potential therapeutic application in patients undergoing bone marrow transplantation.
- Subjects :
- Animals
Anti-Inflammatory Agents metabolism
Anti-Inflammatory Agents pharmacology
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cell Transplantation
Chemokine CCL3 genetics
Chemokine CCL5 metabolism
Dexamethasone pharmacology
Female
Graft vs Host Disease genetics
Graft vs Host Disease prevention & control
Graft vs Leukemia Effect drug effects
Immunohistochemistry
Interferon-gamma metabolism
Intestine, Small immunology
Intestine, Small metabolism
Intestine, Small pathology
Macrophage Inflammatory Proteins genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Mice, Transgenic
Spleen cytology
Chemokine CCL3 deficiency
Graft vs Host Disease metabolism
Macrophage Inflammatory Proteins metabolism
Receptors, Chemokine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 184
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20100934
- Full Text :
- https://doi.org/10.4049/jimmunol.0902614