Differences between neonates and adults in tissue-type-plasminogen activator (t-PA)-catalyzed plasminogen activation with various effectors and in carbohydrate sequences of fibrinogen chains

Our study investigates the effect of fetal and adult soluble fibrin (SF), f etal and adult fibrinogen A alpha -and gamma -chains, as well as adult CNBr -fibrinogen fragments on tissue-type plasminogen activator (t-PA)-catalyzed plasminogen activation of both fetal and adult Glu-plasminogen types 1 and 2. In addition, we determined carbohydrate sequences of fetal and adult B beta- and gamma -chains by mass spectrometric analysis. In the absence of a n effector, no substantial differences in the rate of plasmin formation cou ld be seen between the fetal and adult plasminogen types. In the presence o f an effector, both fetal Glu-plasminogen types revealed lower values for k (cat) app than the respective adult types. No differences could be seen in the values for K-m app. The resulting differences in catalytic efficiencies between the fetal and adult plasminogen types were much less than previous ly reported. No differences could be seen between fetal and adult effectors in stimulating t-PA-catalyzed plasminogen activation. Detailed analyses of the activation kinetics revealed a longer initial phase of slow plasmin fo rmation of both fetal Glu-plasminogen types compared to their respective ad ult types, indicating a slower plasmin-induced modification of CNBr-fibrino gen fragments or SF by fetal plasmin. Mass spectrometric analysis of the N- glycans present on adult and fetal B beta- and gamma -fibrinogen chains sho wed the presence of a major monosialylated biantennary structure with lesse r amounts of the disialylated form. In contrast to previous data, we conclu de that catalytic efficiency of t-PA-catalyzed plasminogen activation in ne onates is only slightly lower than in adults. (C) 2001 Elsevier Science Ltd . All rights reserved.