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. 1997 Sep 1;100(5):986–995. doi: 10.1172/JCI119649

Bone marrow transplantation reproduces the tristetraprolin-deficiency syndrome in recombination activating gene-2 (-/-) mice. Evidence that monocyte/macrophage progenitors may be responsible for TNFalpha overproduction.

E Carballo 1, G S Gilkeson 1, P J Blackshear 1
PMCID: PMC508273  PMID: 9276715

Abstract

Tristetraprolin-deficient [TTP (-/-)] mice exhibit a complex syndrome of myeloid hyperplasia, cachexia, dermatitis, autoimmunity, and erosive arthritis. Virtually the entire syndrome can be prevented by the repeated injection of anti-TNFalpha antibodies (Taylor, G.A., E. Carballo, D.M. Lee, W.S. Lai, M.J. Thompson, D.D. Patel, D.I. Schenkman, G.S. Gilkeson, H.E. Broxmeyer, B.F. Haynes, and P.J. Blackshear. 1996. Immunity. 4:445-454). In the present study, we transplanted bone marrow from TTP (-/-) and (+/+) mice into recombination activating gene-2 (-/-) mice. After a lag period of several months, marrow transplantation from the (-/-) but not the (+/+) mice resulted in the full syndrome associated with TTP deficiency, suggesting that hematopoietic progenitors are responsible for the development of the syndrome. Western blot analysis of supernatants from cultured TTP-deficient macrophages derived from the peritoneal cavity or bone marrow of adult TTP (-/-) mice, or from fetal liver, demonstrated an increased accumulation of TNFalpha after stimulation with LPS compared to control cells, and also increased accumulation of TNFalpha mRNA. This difference was not observed with cultured fibroblasts or T and B lymphocytes. These data suggest that macrophages are among the cells responsible for the effective excess of TNFalpha that leads to the pathology reported in TTP (-/-) animals, and that macrophage progenitors may be involved in the transplantability of this syndrome.

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Selected References

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