Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis.
The Leishmania surface protease gp63 has been identified as a parasite virulence factor. To better define the role of gp63 in Leishmania infectivity, the interaction of recombinant gp63 with complement and complement receptors was examined. On Leishmania, gp63 was not necessary for complement fixation. Complement activation occurred on transfected organisms expressing varying amounts of gp63 and on organisms expressing a mutant form of gp63 devoid of proteolytic activity. However, organisms expressing wild-type gp63 on their surface fixed only small amounts of the terminal complement components and were dramatically more resistant to lysis by complement than were those lacking functional gp63. Organisms expressing wild-type gp63 more rapidly converted C3b on their surface to a form that exhibited the neoantigen of iC3b and interacted avidly with cells expressing Mac-1, the receptor for iC3b. Complement fixation by transfected mammalian cells expressing recombinant Leishmania gp63 on their surface was also examined. The presence of Leishmania gp63 on the surface of these cells converted them into efficient activators of complement. Cells expressing gp63 on their surface fixed complement and bound avidly to the human complement receptors. The proteolytic activity of this molecule was not necessary for complement activation or adhesion to complement receptors. Thus, gp63 may contribute to parasite virulence by exerting a novel type of control over complement fixation. Organisms expressing gp63 can exploit the opsonic properties of complement while avoiding its lytic effects.
Brittingham
A
A
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Morrison
C J
CJ
McMaster
W R
WR
McGwire
B S
BS
Chang
K P
KP
Mosser
D M
DM
D000818:Animals; D000953:Antigens, Protozoan / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D003167:Complement Activation; D006224:Cricetinae; D018014:Gene Transfer Techniques; D006801:Humans; D007891:Leishmania / Q000201:enzymology*; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D008666:Metalloendopeptidases / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D015800:Protozoan Proteins / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics
D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania