Induction of syngeneic graft-versus-host disease in LPS hyporesponsive C3H/HeJ mice

D. L. Flanagan, R. Gross, C. D. Jennings, B. E. Caywood, S. Goes, A. M. Kaplan, J. S. Bryson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Syngeneic GVHD (SGVHD) develops following syngeneic bone marrow transplantation and treatment with cyclosporine A. Previous studies have demonstrated a role for IL-12, IFN-γ, and TNF-α in the development of murine SGVHD. Macrophages can be activated to secrete IL-12 and TNF-α via a T-cell-dependent or T-cell-independent pathway (LPS or bacterial products). Studies were designed to determine if LPS participated in the development of SGVHD in C3H/HeN (LPS-responsive) and C3H/HeJ (LPS-hyporesponsive) mice. C3H/HeJ and C3H/HeN mice had similar levels of disease induction and pathology. Following induction of SGVHD, treatment of C3H/HeN, but not C3H/HeJ, mice with a sublethal dose of LPS resulted in mortality. However, neutralization of IL-12 abrogated the development of disease in C3H/HeJ mice, demonstrating that activated macrophages and their products participated in the development of SGVHD in these animals. These data suggested that LPS responsiveness was not a predisposing factor for SGVHD induction.

Original languageEnglish
Pages (from-to)873-880
Number of pages8
JournalJournal of Leukocyte Biology
Volume70
Issue number6
DOIs
StatePublished - 2001

Keywords

  • Bone marrow transplantation
  • Cyclosporine A
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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