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Interleukin-4 stimulates expression of urokinase-type-plasminogen activator
in cultured human foreskin microvascular endothelial cells
J Wojta, M Gallicchio, H Zoellner, EL Filonzi, JA Hamilton and K McGrath
Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville,
Victoria, Australia.
The effect of interleukin-4 (IL-4) on the fibrinolytic system of human
microvascular and macrovascular endothelial cells in culture was studied.
Only foreskin microvascular endothelial cells (EC) responded to IL-4
treatment with a dose- and time-dependent increase in urokinase- type
plasminogen activator (u-PA) (control: 3.0 +/- 0.8 ng/10(5) cells/24 h; 200
U/mL IL-4: 6.7 +/- 0.8 ng/10(5) cells/24 h), whereas human macrovascular EC
remained unaffected. A maximum effect was achieved with 200 U/mL IL-4.
Little u-PA activity was detected in the conditioned media of human
foreskin microvascular EC (HFMEC) treated without and with IL-4 before
plasmin treatment (control: 0.03 +/- 0.003 IU/10(5) cells/20 h; 200 U/mL
IL-4: 0.09 +/- 0.007 IU/10(5) cells/20 h). These values increased to 0.18
+/- 0.02 IU/10(5) cells/20 h and 0.53 +/- 0.04 IU/10(5) cells/20 h,
respectively, after plasmin treatment, indicating that u-PA is released by
HFMEC predominantly in its inactive precursor form single-chain u-PA
(scu-PA). u-PA activity increased also in the cell lysates of HFMEC up to
2.5-fold after IL-4 treatment. Plasminogen activator inhibitor type-1
(PAI-1) levels produced by HFMEC remained unaffected by IL-4, whereas
tissue-type plasminogen activator (t-PA) levels were slightly decreased
when HFMEC were treated with IL-4. These findings were also reflected in
the specific mRNA levels as determined by Northern blotting. u-PA-specific
mRNA increased significantly in HFMEC in the presence of IL-4, whereas t-PA
mRNA and PAI-1-specific mRNA in HFMEC and u-PA specific mRNA in human
saphenous vein EC (HSVEC) remained unaffected by IL-4 treatment. Our
findings suggest a role for IL-4 in the process of angiogenesis, in
addition to its known proliferative effect on human microvascular EC, by
increasing the fibrinolytic potential of such EC, thereby facilitating
extracellular proteolysis and cell migration.
Volume 81,
Issue 12,
pp. 3285-3292,
06/15/1993
Copyright © 1993 by The American Society of Hematology
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