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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0544.
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Blood, 1 January 2003, Vol. 101, No. 1, pp. 119-123
HEMATOPOIESIS
An intrinsic thyrotropin-mediated pathway of TNF-
production by bone marrow cells
Heuy-Ching Wang,
Jolene Dragoo,
Qin Zhou, and
John R. Klein
From the Department of Basic Sciences, Dental Branch,
University of Texas Health Science Center at Houston.
Recent studies have identified a role for thyroid-stimulating
hormone (TSH; ie, thyrotropin) as an inductive signal for tumor necrosis factor- (TNF- ) secretion by bone marrow (BM) cells, although the features of that activation 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 nonerythroid
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 use 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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