TY - JOUR
T1 - Induction of syngeneic graft-versus-host disease in LPS hyporesponsive C3H/HeJ mice
AU - Flanagan, D. L.
AU - Gross, R.
AU - Jennings, C. D.
AU - Caywood, B. E.
AU - Goes, S.
AU - Kaplan, A. M.
AU - Bryson, J. S.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Bone marrow transplantation
KW - Cyclosporine A
KW - Lipopolysaccharide
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U2 - 10.1189/jlb.70.6.873
DO - 10.1189/jlb.70.6.873
M3 - Article
C2 - 11739549
AN - SCOPUS:0035657020
SN - 0741-5400
VL - 70
SP - 873
EP - 880
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -