Urokinase receptor. An activation antigen in human T lymphocytes.
The ability of activated T lymphocytes to extravasate and reach inflammatory and malignant foci in the tissues is a basic function of cellular immunity. Recent evidence strongly suggests that the urokinase receptor (uPAR) holds a central position in the development of human two-chain urokinase-mediated pericellular proteolysis and matrix degradation, an important element in cell migration. In this report we establish uPAR as a pan T cell activation Ag. As determined by FACS analysis, CD3+ lymphocytes from healthy donors exhibited no significant uPAR expression. In contrast, patients (e.g., HIV-positive donors) showed distinct uPAR expression, confined to HLA-DR+ cells, in up to 80% of all T cells. In vitro activation by PMA caused a rapid up-regulation of membrane uPAR in all healthy donor T cells and was accompanied by enhanced receptor synthesis and elevated uPAR mRNA levels. A similar induction resulted from activation via the TCR/CD3 complex using mitogens (PHA, and Con A), anti-CD3 antibodies, and alloantigen. Receptor expression at single cell level was also modulated by a number of cytokines. IL-2, IL-4 and IL-7 increased uPAR presentation on 20 to 50% of the T cell population, and combined stimulation of bulk cultures demonstrated an additive effect of IL-2 and IL-7, whereas the response to each of the two was inhibited by IL-4. In addition, TGF-beta 1 substantially reduced the uPAR expression in T cell cultures responding to PHA, IL-2, and IL-7. Irrespective of the activating reagent, the T cells appeared to produce the same molecular uPAR species, but the affinity of uPAR expressed in PMA blasts was decreased, presumably because of a differential location at the cell surface. All activated cultures showed co-expression of uPAR and CD25. The finding that the urokinase receptor is an activation Ag may suggest that cell-associated plasminogen activation is involved in extravasation and migration of activated T cells.
Nykjaer
A
A
Institute of Medical Biochemistry, University of Aarhus, Denmark.
Møller
B
B
Todd
R F
RF
Christensen
T
T
Andreasen
P A
PA
Gliemann
J
J
Petersen
C M
CM
D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D017931:DNA Primers; D007376:Interleukin-2; D015851:Interleukin-7; C524898:PLAUR protein, human; D010703:Phorbol Esters; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4