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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2810-2818
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Plasminogen activator inhibitor type 2: a regulator of
monocyte proliferation and differentiation
Hong Yu,
Fabienne Maurer, and
Robert L. Medcalf
From Monash University Department of Medicine, Box Hill
Hospital, Victoria, Australia.
We have explored the role of plasminogen activator inhibitor type 2 (PAI-2) in THP-1 monocyte-like cells. These cells possess a mutation
in the PAI-2 gene and do not produce an active
PAI-2 protein. Transfection of THP-1 cells with plasmids expressing active PAI-2 reduced the cells' inherent adhesive properties and decreased the rate of cell proliferation. THP-1 cells expressing active
PAI-2 also displayed an altered phenotype in response to phorbol
ester-induced differentiation that was concomitant with a reduction in
CD14 expression. THP-1 cells transfected with a variant PAI-2
containing a mutation in the reactive center
(PAI-2Ala380) displayed no noticeable change in any
of these parameters, suggesting the involvement of a PAI-2-sensitive
serine protease(s). The antiproliferative effect of PAI-2 was
attenuated by treating the PAI-2-expressing THP-1 cells with
recombinant urokinase (u-PA), suggesting that PAI-2 was disruptive of a
u-PA/u-PA receptor signaling pathway initiated on the cell surface.
Consistent with this, treatment of wild-type THP-1 cells with
recombinant PAI-2 also caused a reduction in cellular proliferation.
These results implicate endogenous PAI-2 as a modulator of monocyte
adhesion, proliferation, and differentiation.
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