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In vitro stimulatory effect of substance P on hematopoiesis
P Rameshwar, D Ganea and P Gascon
Department of Medicine, University of Medicine and Dentistry-New Jersey
Medical School, Newark 07103.
The neuropeptide Substance P (SP) is widely distributed in the peripheral
nervous system. Its biologic effects have been extensively studied in the
immune system. However, even though the bone marrow (BM) is innervated with
SP-immunoreactive fibers and some of its cells not only express SP
receptors (T and B cells, endothelial cells, and macrophages) but also
produce SP (macrophages, eosinophils, and endothelial cells), the effects
of SP on hematopoiesis are scanty. Furthermore, SP induces the production
of hematopoietic growth factors (HGFs) (interleukin-1 [IL-1], IL-6, and
tumor necrosis factor alpha) from human monocytes. In this study, we have
found a potent in vitro stimulatory effect of SP (10(-8) to 10(-12) mol/L)
on hematopoiesis for both erythroid and granulocytic progenitors in
short-term methyl- cellulose BM cultures. SP alone, in the absence of
exogenous HGFs, is able to sustain hematopoiesis in vitro. This stimulatory
effect of SP is: (1) mostly mediated by the adherent cells; (2) completely
abrogated by two SP receptor (SP-R) antagonists; and (3) partially reduced
by anti-IL-1, IL-3, IL-6, and granulocyte-macrophage colony-stimulating
factor (GM-CSF). Furthermore, it appears that the stimulatory effect of SP
may be mediated by IL-3 and GM-CSF because we have also found that SP
induces the release of these two cytokines from BM mononuclear cells.
Considering that the SP effect occurs at concentrations as low as 10(-11)
mol/L, and via a specific receptor, it appears that SP may play a
physiologic role in regulating hematopoiesis, at least partially through
the adherent BM cells and the release of HGFs, and may place SP, a
neuropeptide, in a new category of hematopoietic regulators.
Volume 81,
Issue 2,
pp. 391-398,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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