The macrophage-attachment glycoprotein gp63 is the predominant C3-acceptor site on Leishmania mexicana promastigotes.
The interaction between Leishmania promastigotes and their vertebrate host's complement system results not only in parasite lysis but also, due to surface-bound complement components, in increased macrophage binding potential. In this study we demonstrate, with the use of isolated complement components, that activation is via the alternative complement pathway, initiated by direct deposition of C3 onto the parasite surface. The predominant C3 acceptor site on the promastigotes was initially identified as the glycoprotein gp63 by anti-C3 antibody immunoprecipitation of radioiodinated promastigotes following incubation in the alternative pathway initiators C3, and factors B and D. The C3-binding properties of gp63 were confirmed and quantified, in relation to other surface antigens, by incubating parasites in iodinated C3 and immunoprecipitating bound C3 with antibodies directed against different promastigote surface antigens. The other abundant surface antigen, the glycolipid 'excreted factor', did not show any C3-binding activity. Further demonstration was provided by incubating liposomes containing either gp63 or excreted factor in iodinated C3 and factors B and D. Only gp63-containing liposomes bound C3. Considering that both gp63 and the excreted factor have recently been implicated in attachment and uptake by macrophage, these findings may have considerable bearing in the determination of which of the macrophage surface receptors identify which parasite ligand.
D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D007894:Leishmania mexicana / Q000276:immunology*; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008854:Microscopy, Electron; D011951:Receptors, Complement / Q000032:analysis
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D003176:Complement C3; D006023:Glycoproteins; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D008715:Methionine