Interaction of Leishmania mexicana promastigotes with the plasminogen-plasmin system.
The binding of human plasminogen and plasmin to the promastigote form of Leishmania mexicana was investigated. L. mexicana was capable to bind both molecules, the binding being inhibited by epsilon-aminocaproic acid. Scatchard plot analysis revealed a dissociation constant (Kd) value of 2.4+/-0.8 microM and 0.9+/-0.1 x 10(4) binding sites per cell for plasminogen and a Kd value of 1.2+/-0.4 microM and 1.6+/-0.2 x 10(5) binding sites per cell for plasmin. C-terminal lysine residues are involved in plasminogen binding to cells, since carboxypeptidase B treatment reduced this binding by 34%. Ligand blotting analysis showed a group of proteins, with molecular masses between 105 and 115 kDa, capable to interact with plasminogen. Zymogram analysis showed that the protease activity acquired by L. mexicana, due to the interaction with either plasminogen or plasmin, comprises an important fraction of the total protease activity at pH 7.7. Plasminogen activation by tissue-type plasminogen activator (t-PA) was enhanced by the presence of L. mexicana promastigotes. These results raise the question whether the interaction of L. mexicana with components of the fibrinolytic system is involved in the virulence of the parasite.
Avilan
L
L
Laboratorio de Immunología de Parasitosis (LABINPAR), Departamento de Biología, Facultad de Ciencias, Universidad de Los Andes, Mérida, Venezuela. avilan@ciens.ula.ve
Calcagno
M
M
Figuera
M
M
Lemus
L
L
Puig
J
J
Rodriguez
A M
AM
D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007894:Leishmania mexicana / Q000254:growth & development / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D015800:Protozoan Proteins; D010958:Plasminogen; D002268:Carboxypeptidases; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator