M. Ries et al., Differences between neonates and adults in the urokinase-plasminogen activator (u-PA) pathway of the fibrinolytic system, THROMB RES, 100(4), 2000, pp. 341-351
This study deals with plasminogen activation kinetics of fetal and adult Gl
u-plasminogen types 1 and 2 as well as fetal and adult Lys-plasminogen by u
rokinase in the presence and absence of the lysine analogues epsilon -amino
-n-caproic acid (EACA) and tranexamic acid. In addition, activation kinetic
s of single-chain urokinase-plasminogen activator (scu-PA) by adult and fet
al plasmin types were investigated in the absence and presence of soluble f
ibrin. All Lys-plasminogen isoforms were more readily activated by urokinas
e than their corresponding Glu-plasminogen types. No substantial difference
s of the catalytic constants of urokinase-catalyzed plasminogen activation
could be obtained when all fetal plasminogen types were compared to the res
pective adult types. In the case of all Glu-plasminogen isoforms, EACA as w
ell as tranexamic acid first stimulated the activation process and, at high
er concentrations, showed inhibitory properties. Again, the relative abilit
y of all fetal plasminogen types to interact with lysine analogues revealed
no differences compared to the respective adult glycoforms. In the absence
of soluble fibrin, the catalytic efficiency of scu-PA activation by plasmi
n was significantly lower for both fetal plasmin isoforms. However, there w
ere no differences in catalytic efficiency between fetal and adult plasmin
types in the presence of 4 muM soluble fibrin. In conclusion, no substantia
l differences exist in urokinase-catalyzed plasminogen activation between n
eonates and adults, which is in contrast to reported data on plasminogen ac
tivation by tissue-type plasminogen activator. In the absence of soluble fi
brin, scu-PA activation by fetal plasmin is markedly slower than by adult p
lasmin. However, this is compensated when fibrin is added at a concentratio
n that is close to the physiological fibrinogen concentration in plasma. It
can be summarized that the differences in carbohydrate structures of fetal
and adult plasminogen are not associated with major differences in the glo
bal function of this part of fibrinolysis, despite functional alterations o
f scu-PA activation. (C) 2000 Elsevier Science Ltd. All rights reserved.