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Macrophage colony-stimulating factor and granulocyte-macrophage colony-
stimulating factor stimulate the synthesis of plasminogen-activator
inhibitors by human monocytes
JA Hamilton, GA Whitty, H Stanton, J Wojta, M Gallichio, K McGrath and G Ianches
Department of Medicine, University of Melbourne, Australia.
Macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-
macrophage CSF (GM-CSF) have been shown to increase human monocyte
urokinase-type plasminogen-activator (u-PA) activity with possible
consequences for cell migration and tissue remodeling; because monocyte
u-PA activity is likely to be controlled in part also by the PA inhibitors
(PAIs) made by the cell, the effect of M-CSF and GM-CSF on human monocyte
PAI-2 and PAI-1 synthesis was investigated. To this end,
elutriation-purified human monocytes were treated in vitro with purified
recombinant human M-CSF and GM-CSF, and PAI-2 and PAI-1 antigen and mRNA
levels measured by specific enzyme-linked immunosorbent assays and Northern
blot, respectively. Each CSF could enhance the protein and mRNA levels of
PAI-2 and PAI-1 at similar concentrations for each product. This similar
regulation of monocyte PAI expression in response to the CSFs contrasted
with that found for the effects of lipopolysaccharide, transforming growth
factor-beta and a glucocorticoid. Therefore, PAIs may be modulating the
effects of the CSFs on monocyte u-PA activity at sites of inflammation and
tissue remodeling.
Volume 82,
Issue 12,
pp. 3616-3621,
12/15/1993
Copyright © 1993 by The American Society of Hematology
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