Receptors for carbohydrate ligands including heparin on the cell surface of Leishmania and other trypanosomatids

Abstract

SummaryBy employing neoglycoproteins (NGP) and glycosaminoglycans, the detection of endogenous glycoligand-binding sites has become possible. Monitoring specific binding of I I of these sugar receptor-specific tools, 13 trypanosomatids of monogenetic genera Blastocrithidiu, Crithidiu, Herpetomonas, and Leptomonas and digenetic genera Endotrypanurn, Leishmania, and Satrroleishmania were analysed by agglutination and fluorescence assays. NGP showed agglutination reactions only with the digenetic but not with the monogenetic species. Sensitive flow cytofluorimetric investigations revealed that the apparently different reactivity to NGP is due to a pronounced quantitative difference in expression of binding sites between mono-and digenetic flagellates. Moreover, flow cytofluorimetry was used to demonstrate the occurrence of receptor sites for heparin on the cell surfaces of all trypanosomatids. An indication for a correlation of the binding capacity for the NGP N-acetyi-P-D-glucosamine and heparin to differences in the pathogenicity of parasites was observed for Leishmania donovani as well as Leishmania enriettii. Infective populations of these species contained a significantly higher number of cells which had bound N-acetyl-P-D-glucosamine and heparin than noninfective (long-term in vitro-cultured) populations. T h e results of the present report additionally support the hypothesis that lectin-carbohydrate interactions with neutral sugar moieties and heparin or heparin-like molecules participate in the interactions between trypanosomatids and host (cells), and that the detected binding sites for carbohydrates and heparin may thus be referred to as potential virulence factors.keywords flagellate, Leishmania, Trypanosomatidae, lectin, neoglycoprotein, heparin correspondence Prof. J. Schottelius, Section

Eukaryotic glycosylation: whim of nature or multipurpose tool?

“…This receptor-directed activity does not only encompass the famous textbook example of serpin binding by the heparin pentasaccharide shown in figure 20. Also, a variety of proteins including laminin, thrombospondin, fibronectin, cell adhesion molecules such as N-CAM, lectins and virulence factors are proven binding partners for the sugar part of proteoglycans [298,371,372,[413][414][415][416][417][418][419][420][421]. This property is likewise relevant for cytokines and growth factors.…”

Leishmania (Viannia) braziliensis: insights on subcellular distribution and biochemical properties of heparin-binding proteins

“…HBPs have been associated with the infective forms of L. (L.) donovani, as they predominate on the surface of stationary-phase promastigotes from recently isolated samples. However, subsequent passages of parasites in culture have led to the loss of the heparinbinding abilities of the parasites (Butcher et al 1992;Kock et al 1997).…”

Characterization of a midgut mucin-like glycoconjugate of Lutzomyia longipalpis with a potential role in Leishmania attachment

“…We may speculate that the parasite receptor for the 45 kDa glycoconjugate is a lectin-like molecule with predicted specificity for GalNAc, mimicking the activity of HPA lectin. Lectin activities and heparin-binding activities were demonstrated in Leishmania promastigotes by various authors [ 24 – 28 ]. More recent studies suggest that 65 kDa and 55 kDa heparin-binding proteins from the surface of L. braziliensis promastigotes can be involved in parasite adhesion to Lu.…”