Plasminogen-mediated group A streptococcal adherence to and pericellular invasion of human pharyngeal cells.

Alpha-enolase (SEN) is a strong plasminogen-binding protein on the surface of group A streptococci (GAS). By flow cytometry and immunofluorescence analyses and using human enolase-specific antibody, human pharyngeal cells (Detroit 562) also were found to express enolase on their surface. Detroit 562 cells preferentially bound to Lys-plasminogen and this binding was inhibited in the presence of a lysine analog, epsilon-aminocaproic acid and by carboxypeptidase-B treatment suggesting that the C-terminal lysine residue of the putative pharyngeal cell receptor(s) may play an important role in plasminogen-binding. The increased plasminogen-binding in the presence of free enolase indicated the presence of an enolase/SEN-specific receptor on the pharyngeal cell surface. GAS, when precoated with Lys-plasminogen, adhered to pharyngeal cells significantly more in numbers than when precoated with fibronectin or laminin. Similarly, GAS adhered also significantly more in numbers to pharyngeal cells which were precoated with Lys-plasminogen. GAS adhered similarly in high numbers when incubated with pharyngeal cells in the presence of soluble plasminogen. The de novo pharyngeal cell-bound protease activity, created as a result of activation of bound plasminogen by t-PA, indicated its potential role in pericellular fibrinolytic activity. Further GAS with tPA-activated plasminogen bound on their surface penetrated through Transwell-grown pharyngeal cells in significantly higher numbers. Together, the results presented in this study highlight a novel function of plasminogen in streptococcal adherence to pharyngeal cells and a newly discovered streptococcal ability to pericellularly invade pharyngeal cells as a result of tPA/endogenous plasminogen activator-mediated proteolytic activity.