Titre
Plasminogen activator inhibitor type 2: a regulator of monocyte proliferation and differentiation
Type
article
Institution
Externe
Périodique
Auteur(s)
Yu, H.
Auteure/Auteur
Maurer, F.
Auteure/Auteur
Medcalf, R. L.
Auteure/Auteur
Liens vers les personnes
ISSN
0006-4971
Statut éditorial
Publié
Date de publication
2002-04
Volume
99
Numéro
8
Première page
2810
Dernière page/numéro d’article
8
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Apr 15
Résumé
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-2(Ala380)) 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.
Sujets
PID Serval
serval:BIB_4245A1446D60
PMID
Open Access
Oui
Date de création
2008-01-25T13:19:38.915Z
Date de création dans IRIS
2025-05-20T19:47:20Z