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MJ Hannocks, L Oliver, JL Gabrilove and EL Wilson
Department of Cell Biology, New York University Medical Center, NY 10016.
Plasminogen activators (PAs) and/or plasmin may be involved in
hematopoietic regulation. These enzymes release biologically relevant
cytokines such as basic fibroblast growth factor (bFGF) from matrix and
cell surfaces. In addition, transforming growth factor beta (TGF beta) and
interleukin-1 beta (IL-1 beta) are converted from inactive to active forms
by plasmin. Therefore, we studied the regulation of PAs and their specific
inhibitors, PA inhibitor 1 (PAI-1) and PA inhibitor 2 (PAI-2), in human
bone marrow stromal fibroblasts by IL-1 beta, bFGF, and TGF beta. All three
cytokines stimulated PA secretion. IL-1 beta at 10(4) U/mL increased
urokinase (u-PA) levels approximately 10-fold, bFGF at 0.2 ng/mL also
increased production 10-fold, but increased predominantly tissue PA (t-PA)
expression. TGF beta at 0.2 ng/mL increased u-PA production up to 300-fold.
PAI-1 and PAI-2 are also regulated by these cytokines. IL-1 beta decreased
PAI-1 levels by 50% and stimulated PAI-2 levels sixfold. bFGF had minimal
effects on PAI-1 and TGF beta increased PAI-1 levels twofold. Neither of
these agents had an effect on PAI-2 levels. Thus, three cytokines relevant
to bone marrow physiology regulate PA and inhibitor production by human
bone marrow stromal fibroblasts. In this manner PA and plasmin generation
in specific microenvironments in the bone marrow may be one of the factors
orchestrating the complex series of events, which results in an efficient
exquisitely regulated hematopoietic process.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
