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Infection and Immunity, September 1999, p. 4477-4484, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interaction of Leishmania gp63 with Cellular Receptors for Fibronectin

Andrew Brittingham,1,dagger Gang Chen,1 Bradford S. McGwire,2 Kwang-Poo Chang,2 and David M. Mosser1,*

Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140,1 and the Department of Microbiology and Immunology, Finch University of the Health Sciences, Chicago Medical School, North Chicago, Illinois 600642

Received 13 November 1998/Returned for modification 5 January 1999/Accepted 16 June 1999

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 alpha 4/beta 1 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 alpha 4/beta 1 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 beta 1 integrins, because pretreatment of macrophages with monoclonal antibodies to the beta 1 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 beta 1 integrins, which recognize fibronectin-like molecules such as gp63 on the surface of the parasite.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Temple University School of Medicine, 3400 N. Broad St., Philadelphia, PA 19140. Phone: (215) 707-8262. Fax: (215) 707-7788. E-mail: dmmosser{at}astro.temple.edu.

dagger Present address: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242.

Infection and Immunity, September 1999, p. 4477-4484, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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