Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation

Patricia Ewing, Gerhard C. Hildebrandt, Simone Planke, Reinhard Andreesen, Ernst Holler, Armin Gerbitz

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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→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 protoporphyrine 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 γ 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 α 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.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalInternational Journal of Molecular Medicine
Volume20
Issue number3
DOIs
StatePublished - Sep 2007

Keywords

  • Allogeneic bone marrow transplantation
  • Antigen presenting cells
  • Cobalt protoporphyrine
  • Heme oxygenase-1

ASJC Scopus subject areas

  • Genetics

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