ENHANCEMENT OF T-PA-MEDIATED PLASMINOGEN ACTIVATION BY BACTERIAL SURFACE-RECEPTORS

A total of 63 strains representing 7 species of plasminogen binding ba cteria, were examined for the ability to potentiate t-PA and urokinase (u-PA) mediated activation of human plasminogen to plasmin. Tested sp ecies included beta-haemolytic streptococci groups A, C, and G, Strept ococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Proteus mirabilis. The effect on plasminogen activation was measured using a coupled enzymatic assay with a chromogenic substrate. The chan ges in absorbance were found to be linear functions of t(2) in agreeme nt with theoretical expectations. Most plasminogen binding strains wer e capable to dramatically enhance the rate of t-PA induced plasminogen activation. The most pronounced potentiation was observed with a Stre ptococcus equisimilis strain which increased the activation rate 130-f old. High potentiations was also detected for N. meningitidis and S. p neumoniae strains, P. mirabilis was an exception as some strains were capable to bind plasminogen without any influence on plasminogen activ ation. Aslo, u-PA mediated plasminogen activation was enhanced in the presence of bacteria, However the stimulation factor obtained were in most strains much less than those obtained with t-PA. For different st rains within a species, the capability to enhance the rate of the t-PA mediated activation correlated with plasminogen binding (r=0.74-0.92) . Both plasminogen binding and the stimulation of plasminogen activati on were abolished in the presence of 6-aminohexanoic acid (6-AHA, epsi lon-aminocaproic acid) suggesting that the lysine-binding sites in the plasminogen molecule are involved in both phenomena. The binding of p lasminogen and facilitation of its activation provide bacteria with an active proteolytic shield of possible importance in tissue penetratio n and infection.