Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease Journal Article
| Authors: | Lu, S. X.; Holland, A. M.; Na, I. K.; Terwey, T. H.; Alpdogan, O.; Bautista, J. L.; Smith, O. M.; Suh, D.; King, C.; Kochman, A.; Hubbard, V. M.; Rao, U. K.; Yim, N.; Liu, C.; Laga, A. C.; Murphy, G.; Jenq, R. R.; Zakrzewski, J. L.; Penack, O.; Dykstra, L.; Bampoe, K.; Perez, L.; Furie, B.; van den Brink, M. R. M. |
| Article Title: | Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease |
| Abstract: | Alloreactive T cells are crucial for graft-versus-host disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report in this paper that P-selectin, a glycoprotein found on resting and inflamed endothelium, is important for donor alloreactive T cells trafficking into GVHD target organs, such as the intestines and skin. Compared with wild-type (WT) recipients of allogeneic bone marrow transplantation, P-selectin-/- recipients exhibit decreased GVHD mortality and decreased GVHD of the skin, liver, and small bowels. This was associated with diminished in-filtration of alloactivated T cells into the Peyer's patches and small bowels, coupled with increased numbers of donor T cells in the spleen and secondary lymphoid organs (SLOs). Surprisingly, however, donor T cells deficient for P-selectin glycoprotein ligand 1, the most well described P-selectin ligand, mediated GVHD similar to WT T cells and accumulated in SLO and target organs in similar numbers as WT T cells. This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO and that donor T cells may use multiple P-selectin ligands apart from P-selectin glycoprotein ligand 1 to interact with P-selectin and traffic into inflamed tissues during GVHD. We conclude that targeting P-selectin may be a viable strategy for GVHD prophylaxis or treatment. Copyright © 2010 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; protein expression; transplantation, homologous; genetics; nonhuman; pathophysiology; t lymphocyte; animal cell; mouse; animal; metabolism; mouse mutant; animals; mice; mice, knockout; animal tissue; apoptosis; animal experiment; animal model; inflammation mediators; allogenic bone marrow transplantation; in vivo study; protein interaction; in vitro study; pathology; transplantation; mice, inbred balb c; mice, inbred c57bl; physiology; c57bl mouse; disease model; immunology; lymphocyte activation; bagg albino mouse; vascular endothelium; endothelium, vascular; membrane glycoproteins; membrane protein; ligand; graft versus host reaction; ligands; upregulation; t-lymphocyte subsets; disease models, animal; bone marrow transplantation; graft vs host disease; small intestine; cell separation; t lymphocyte subpopulation; graft recipient; allotransplantation; endothelial leukocyte adhesion molecule 1; p-selectin; padgem protein; p selectin glycoprotein ligand 1; autacoid; p selectin ligand protein; p-selectin ligand protein; peyer patch |
| Journal Title: | Journal of Immunology |
| Volume: | 185 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2010-08-01 |
| Start Page: | 1912 |
| End Page: | 1919 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0903148 |
| PUBMED: | 20622117 |
| PROVIDER: | scopus |
| PMCID: | PMC3752704 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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