Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased glycosylation of the protein.

Abstract

Plasminogen isolated from 60 full-term newborns differs from adult plasminogen in carbohydrate composition, kinetic activation constants, and cell binding. Amino acid composition and amino-terminal sequence analysis data indicate that the plasminogens of neonates and adults have the same amino acid sequence. Like the adult, the neonate has two glycoforms, but both have significantly more mannose and sialic acid than the adult forms. The difference in the neonatal glycosylation is probably responsible for the altered migration observed by isoelectric focusing. Moreover, the difference in carbohydrate composition appears to be the basis of the decreased functional activity of the neonatal plasminogen. The k,,,t/K, ratios indicate that the overall activation rates of the two neonatal plasminogen glycoforms are lower compared with the adult glycoforms. In addition, neonatal plasminogen does not bind as well to cellular receptors compared with adult plasminogen. These studies suggest a basis for the decreased fibrinolytic activity observed in neonates. (J. Clin. Invest. 1990. 86:107-112.)

Evidence for a Novel O-Linked Sialylated Trisaccharide on Ser-248 of Human Plasminogen 2

“…Davidson and Castellino (9) have shown that differently glycosylated forms of Pg exhibit different kinetic parameters for activation by uPA. In addition, neonatal Pg 2, which has 18 times more NeuNAc than adult Pg 2, is activated 6-fold less efficiently by tPA (10). Pg 2 also binds to cell surfaces with greater affinity than the more glycosylated Pg 1 (11).…”

The influence of the nature of the asparagine 289-linked oligosaccharide on the activation by urokinase and lysine binding properties of natural and recombinant human plasminogens.

“…This clinical state has been correlated with the altered glycosylation of neonatal HPg, wherein one glycoform that is heavily mannosylated and another that is extensively polysialylated have been isolated from neonatal plasma (24). Both ofthe neonatal glycoforms exhibit weaker binding to cellular receptors on U937 cells than adult HPg, and also display defective steady-state activation kinetic parameters in a tissue-type plasminogen activator/ fibrinogen fragment activation system (24).…”

The Influence of Age on in vitro Plasmin Generation in the Presence of Fibrin Monomer

“…However, differences in glycosylation between fetal and adult plasminogen have also been associated with decreased activation rate of fetal plasminogen to plasmin [26]. Reported functional findings include the fact that there is less binding of both fetal plasminogen glycoforms to cellular receptors and that there is lower catalytic efficiency (kcat/K m ) of the activation of the two fetal plasminogen types by tPA [33]. Binding of plasmin to α 2 M provided a significant portion of the plasmin inhibition, especially in the case of cord plasma.…”

“…It has been observed that newborns have significantly lower plasminogen and HRG levels when compared with those of adults [25]. In another study, plasminogen isolated from 60 full-term newborns differed from adult plasminogen in carbohydrate composition, kinetic activation constants, and cell binding [26]. Differences in all these parameters suggested a basis for the decreased fibrinolytic activity observed in neonates.…”