Regulation of the uPAR/uPA system expressed on monocytes by the deactivating cytokines, IL-4, IL-10 and IL-13: consequences on cell adhesion to vitronectin and fibrinogen.
Urokinase (uPA) and its receptor (uPAR) have been proposed to be involved in monocyte migration by inducing degradation of matrix proteins. In addition, uPAR is also implicated in cell adhesion to the vascular wall. The adhesive function of uPAR depends on a direct interaction with vitronectin which is increased by uPA and by modification of cell surface integrin (such as CD11b-CD18) when associated to uPAR. In this study we analysed the role of three deactivating cytokines, IL-4, IL-10 and IL-13, on the surface expression of uPA, uPAR and CD11b by monocytes and their consequences on monocyte adhesion to immobilized fibrinogen and vitronectin. IL-10 induced a decrease in uPA and CD11b after 18 h incubation and a delayed decrease in uPAR which was only significant after 48 h incubation. These results may explain the decrease in monocyte adhesion, which was observed after an 18 h incubation with IL-10, on immobilized vitronectin and fibrinogen. In contrast, IL-4 and IL-13 induced a decrease in uPAR after 18 h and a significant increase in uPA both in the cell lysates and at the cell surface, as well as an increase in cell surface associated CD11b. These cytokines did not modify cell adhesiveness to vitronectin or fibrinogen despite the increase in CD11b-CD18. This could be due to the decrease in uPAR because CD11b-CD18/uPAR forms a cell adhesion complex. In addition, the increase in uPA induced by IL-4 could counterbalance the direct interaction of uPAR with vitronectin. The increase in uPA suggests that IL-4 and IL-13 could induce plaque fissuring by monocytes, whereas IL-10 may induce protection against matrix protein degradation by decreasing uPA.
Paysant
J
J
Laboratoire DIFEMA, Faculté de Médecine et de Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Vasse
M
M
Soria
J
J
Lenormand
B
B
Pourtau
J
J
Vannier
J P
JP
Soria
C
C
D002448:Cell Adhesion; D002465:Cell Movement; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism*
D018793:Interleukin-13; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D016753:Interleukin-10; D015847:Interleukin-4; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator