Sequential Expression of Adhesion and Costimulatory Molecules in Graft-versus-Host Disease Target Organs after Murine Bone Marrow Transplantation across Minor Histocompatibility Antigen Barriers

Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, cost...

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Bibliographic Details
Published in:Biology of blood and marrow transplantation 2005-05, Vol.11 (5), p.371-382
Main Authors: Eyrich, Matthias, Burger, Gudrun, Marquardt, Katja, Budach, Wilfried, Schilbach, Karin, Niethammer, Dietrich, Schlegel, Paul G.
Format: Article
Language:English
Subjects:
Adhesion molecules
Animals
Antigens, CD - genetics
Apoptosis - genetics
Apoptotic markers
B7-1 Antigen - genetics
B7-2 Antigen
Bone Marrow Transplantation - adverse effects
Bone Marrow Transplantation - methods
Cell Adhesion Molecules - genetics
Chemotaxis, Leukocyte
Costimulatory molecules
Gene Expression Regulation - physiology
Graft vs Host Disease - etiology
Graft vs Host Disease - immunology
Graft vs Host Disease - pathology
GVHD
Membrane Glycoproteins - genetics
Mice
Mice, Inbred BALB C
Minor Histocompatibility Antigens
Murine model
Organ specificity
Transplantation, Homologous
Transplantation, Isogeneic
Up-Regulation
Whole-Body Irradiation
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Summary:Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon, skin, and liver) after transplantation across minor histocompatibility barriers (B10.D2 → BALB/c, both H-2 d). To distinguish changes induced by the conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic transplant recipients (BALB/c → BALB/c) and irradiated nontransplanted mice were added as controls. Irradiation upregulated the expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in syngeneic mice these effects were reversed from day 9 on, allogeneic recipients showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on day 22, when GVHD became clinically evident. Infiltration of CD4 + and CD8 + donor T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon. Surprisingly, the expression of several other adhesion molecules, such as ICAM-2, platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers were balanced in GVHD organs with the exception of spleen, in which a preferential expression of the proapoptotic Bax could be noted. Our results indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2 provides early costimulatory signals to incoming donor T cells in the intestine, followed by a cascade of proinflammatory signals in other organs once the alloresponse is established.
ISSN:1083-8791
1523-6536
DOI:10.1016/j.bbmt.2005.02.002