Interaction of Leishmania gp63 with Cellular Receptors for Fibronectin

AUTOR(ES)

Brittingham, Andrew

FONTE

American Society for Microbiology

RESUMO

The most abundant protein on the surface of the promastigote form of the protozoan parasites Leishmania spp. is a 63-kDa molecule, designated gp63 or leishmanolysin. Because gp63 has been shown to possess fibronectin-like properties, we examined the interaction of gp63 with the cellular receptors for fibronectin. We measured the direct binding of Leishmania to human macrophages or to transfected mammalian cells expressing human fibronectin receptors. Leishmania expressing gp63 exhibited modest but reproducible adhesion to human macrophages and to transfected CHO cells expressing α4/β1 fibronectin receptors. In both cases, this interaction depended on gp63 but occurred independently of the SRYD sequence of gp63, because parasites expressing gp63 with a mutated SRYD sequence bound to macrophages and α4/β1 receptor-expressing cells as well as did wild-type parasites. The contribution of gp63 to parasite adhesion was more pronounced when the assays were performed in the presence of complement, suggesting that the receptors for complement and fibronectin may cooperate to mediate the efficient adhesion of parasites to macrophages. The interaction of gp63 with fibronectin receptors may also play an important role in parasite internalization by macrophages. Erythrocytes to which gp63 was cross-linked were efficiently phagocytized by macrophages, whereas control erythrocytes opsonized with complement alone bound to macrophages but remained peripherally attached to the outside of the cell. Similarly, parasites expressing wild-type gp63 were rapidly and efficiently phagocytized by resting macrophages, whereas parasites lacking gp63 were internalized more slowly. This rapid internalization of gp63-expressing parasites was dependent on the β1 integrins, because pretreatment of macrophages with monoclonal antibodies to the β1 integrins decreased the internalization of gp63-expressing parasites. These observations indicate that complement receptors are the primary mediators of parasite adhesion; however, maximal parasite adhesion and internalization may require the participation of the β1 integrins, which recognize fibronectin-like molecules such as gp63 on the surface of the parasite.

Documentos Relacionados

• Migration through the Extracellular Matrix by the Parasitic Protozoan Leishmania Is Enhanced by Surface Metalloprotease gp63
• Antibodies raised against synthetic peptides from the Arg-Gly-Asp-containing region of the Leishmania surface protein gp63 cross-react with human C3 and interfere with gp63-mediated binding to macrophages.
• Developmental changes in the expression of Leishmania chagasi gp63 and heat shock protein in a human macrophage cell line.
• Episomal Expression of Specific Sense and Antisense mRNAs in Leishmania amazonensis: Modulation of gp63 Level in Promastigotes and Their Infection of Macrophages In Vitro
• Complex between glycoproteins gI and gp63 of pseudorabies virus: its effect on virus replication.