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| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | International journal of molecular medicine | ||||||||||||||||||||||||||||||||||||||||||
| Volume: | 20 | ||||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 3 | ||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 301-8 | ||||||||||||||||||||||||||||||||||||||||||
| Date: | 2007 | ||||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||||||||||||||||||||||||||||||||||||||||
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Yes | ||||||||||||||||||||||||||||||||||||||||||
| Item ID: | 14498 |
Abstract
Acute graft-versus-host disease (aGvHD) remains the major cause of mortality after allogeneic stem cell transplantation. Acute GvHD can be partially prevented when heme oxygenase-1 (HO-1) is induced in the recipient prior to transplantation but the mechanisms are not fully understood. Using a murine haploidentical bone marrow transplantation (BMT) model (C57Bl/6 right curved arrow B6D2F1) we ...
Abstract
Acute graft-versus-host disease (aGvHD) remains the major cause of mortality after allogeneic stem cell transplantation. Acute GvHD can be partially prevented when heme oxygenase-1 (HO-1) is induced in the recipient prior to transplantation but the mechanisms are not fully understood. Using a murine haploidentical bone marrow transplantation (BMT) model (C57Bl/6 right curved arrow B6D2F1) we tested whether HO-1 induction altered the alloreactive T cell response or rather modulated the inflammatory cytokine profile early after BMT. In vivo administration of cobalt protoporphyrin IX (CoPP) did not affect the expression of MHC class I and II or the costimulatory molecules CD80 and CD86 on murine peritoneal and on splenic dendritic cells (DCs). Allospecific T cell proliferation and interferon gamma secretion did not differ in mixed lymphocyte reactions using either CoPP-pretreated allogeneic recipients or control-treated DCs as stimulators. Furthermore, splenic DCs, isolated one to four days after BMT from CoPP-pretreated recipients did not show any differences in the expression of costimulatory molecules compared to untreated controls, and T cell expansion and the cytolytic capacity 14 days after BMT were equal in the control and CoPP-treated allogeneic groups. Serum tumor necrosis factor alpha levels were significantly reduced in CoPP-treated allogeneic recipients when compared to allogeneic controls and did not differ from the syngeneic recipients. Our results indicate that the protective effects of CoPP-mediated HO-1 induction on survival and aGvHD after allogeneic BMT involve a reduction in the proinflammatory cytokine milieu rather than alteration in allospecific T cell stimulation.
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