A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans.
The intracellular amastigote form of leishmania is responsible for the cell-to-cell spread of leishmania infection in the mammalian host. In this report, we identify a high-affinity, heparin-binding activity on the surface of the amastigote form of leishmania. Amastigotes of Leishmania amazonensis bound approximately 120,000 molecules of heparin per cell, with a Kd of 8.8 x 10(-8) M. This heparin-binding activity mediates the adhesion of amastigotes to mammalian cells via heparan sulfate proteoglycans, which are expressed on the surface of mammalian cells. Amastigotes bound efficiently to a variety of adherent cells which express cell-surface proteoglycans. Unlike wild-type CHO cells, which bound amastigotes avidly, CHO cells with genetic deficiencies in heparan sulfate proteoglycan biosynthesis or cells treated with heparitinase failed to bind amastigotes even at high parasite-input dosages. Cells which express normal levels of undersulfated heparan bound amastigotes nearly as efficiently as did wild-type cells. The adhesion of amastigotes to wild-type nonmyeloid cells was almost completely inhibited by the addition of micromolar amounts of soluble heparin or heparan sulfate but not by the addition of other sulfated polysaccharides.l Binding of amastigotes to macrophages, however, was inhibited by only 60% after pretreatment of amastigotes with heparin, suggesting that macrophages have an additional mechanism for recognizing amastigotes. These results suggest that leishmania amastigotes express a high-affinity, heparin-binding activity on their surface which can interact with heparan sulfate proteoglycans on mammalian cells. This interaction may represent an important first step in the invasion of host cells by amastigotes.
Love
D C
DC
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Esko
J D
JD
Mosser
D M
DM
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006493:Heparin / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D007891:Leishmania / Q000378:metabolism / Q000502:physiology*; D018320:Leishmania major / Q000378:metabolism / Q000502:physiology; D007894:Leishmania mexicana / Q000378:metabolism / Q000502:physiology; D016296:Mutagenesis; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011869:Radioligand Assay
D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; D011509:Proteoglycans; C074285:heparin-binding protein (Leishmania); D006493:Heparin