Bacterial plasminogen receptors: in vitro evidence for a role in degradation of the mammalian extracellular matrix.
The potential of bacterium-bound plasmin to degrade mammalian extracellular matrix and to enhance bacterial penetration through basement membrane was assessed with the adherent strain SH401-1 of Salmonella enterica serovar Typhimurium. Typhimurium SH401-1 was able to bind plasminogen and to enhance the tissue-type plasminogen activator-mediated activation of the single-chain plasminogen to the two-chain plasmin. The end product, the enzymatically active, bacterium-bound plasmin activity, was also formed in a normal human plasma milieu in the presence of exogenous tissue-type plasminogen activator, indicating that plasmin was protected from the plasminogen activator inhibitors and plasmin inhibitors of plasma. Plasmin bound on Typhimurium cells degraded 125I-labeled laminin as well as 3H-labeled extracellular matrix prepared from the human endothelial cell line EA.hy926. The degradations were not seen with Typhimurium cells without plasminogen and were inhibited by the low-molecular-weight plasmin inhibitor aprotinin. Plasmin bound on Typhimurium cells also potentiated penetration of bacterial cells through the basement membrane preparation Matrigel reconstituted on membrane filters. The results give in vitro evidence for degradation of the mammalian extracellular matrix by bacterium-bound plasmin and for a pathogenetic role for bacterial plasminogen receptors.
Lähteenmäki
K
K
Department of General Microbiology, University of Helsinki, Finland.
Virkola
R
R
Pouttu
R
R
Kuusela
P
P
Kukkonen
M
M
Korhonen
T K
TK
D005109:Extracellular Matrix / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D012475:Salmonella / Q000472:pathogenicity*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin