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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0544. This Article Full Text (PDF) All Versions of this Article: 2002-02-0544v1 101/1/119    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, H.-C. Articles by Klein, J. R Search for Related Content PubMed PubMed Citation Articles by Wang, H.-C. Articles by Klein, J. R Social Bookmarking                   What's this? Submitted February 19, 2002 Accepted June 11, 2002 An intrinsic thyrotropin-mediated pathway of TNF production by bone marrow cells Heuy-Ching Wang, Jolene Dragoo, Qin Zhou, and John R Klein* Department of Basic Sciences, University of Texas Health Science Center, Houston, TX, USA * Corresponding author; email: John.R.Klein{at}uth.tmc.edu. Recent studies have identified a role for thyroid stimulating hormone (TSH, i.e., thyrotropin) as an inductive signal for tumor necrosis factor- (TNF) secretion by bone marrow (BM) cells, though the features of that activational pathway have not been defined. Using intracellular TSH staining and enzyme-linked immunoassay for detection of secreted TSH, we demonstrate that TSH synthesis in BM cells occurs within CD45+ (leukocyte-common antigen)hematopoietic cells, and that the majority of that activity resides in a component of CD11b+ BM cells that are not mature T cells, B cells, or Thy-1+ cells in the BM. Conversely, TSH-responsive BM cells defined by expression of TSH receptor (TSHR) using flow cytometry were selectively associated with a non-erythroid CD11b- lymphocyte precursor population. In vitro culture of magnetic-activated cell sorted CD11b- and CD11b+ cells with titrated amounts of purified TSH resulted in significantly higher levels of TNF secretion from CD11b- BM cells compared to non-TSH-treated cells, with no appreciable change in TNF production from CD11b+ cells. These findings are the first to demonstrate TSH production by BM hematopoietic cells, and they demonstrate that TSH may be involved in the regulation of TNF by CD11b- BM cells. They also indicate that TSH-mediated regulation of TNF secretion within the BM most likely operates through an intrinsic network of TSH production and utilization between different types of BM cells, and they suggest that local TSH may be an important homeostatic regulator of hematopoiesis mediated by TNF. 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