Possible Role of the 34-Kilodalton Hyaluronic Acid-Binding Protein in Visceral Leishmaniasis

Abstract

Leishmania donovani, the causative organism of human visceral leishmaniasis, invades host macrophages through its interaction with the cell surface molecules of target cells. The presence of a cell surface protein (Mr 34 kDa) having specific affinity toward hyaluronan (HA), a major extracellular matrix component, has been previously reported in macrophage cell lines. In order to identify the possible role of this HA-binding protein (HABP) in leishmaniasis, initially we demonstrated its overexpression in spleen, liver, macrophages, and serum of hamsters infected with L. donovani. We further observed higher levels of HABP in the macrophage cell line J774.G8 upon infection with L. donovani. Finally, we observed a significant increase in the level of HABP in the serum of patients with kala-azar. In order to understand its functional role in leishmaniasis, we report here a significant inhibition of cellular phosphorylation of HABP in hamster macrophages infected with L. donovani. Interestingly, the 34-kDa HABP was shown to bind with 2 proteins of promastigotes as well as amastigotes of L. donovani (with molecular masses of 55 kDa and 30 kDa respectively), suggesting a possible role for HABP in adhesion during the interaction of promastigotes and macrophages.

Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging

“…It is thus not relevant to automatically infer from the experimentally proven ability of Leishmania parasites to bind heparin that they also bind to heparan sulfate and to heparan sulfate proteoglycans at the host cell surface and that these proteoglycans play a role in Leishmania adhesion to and/or entry into host cells. High-molecular-weight hyaluronan binds to 75% of L. donovani strains, in agreement with the overexpression of a hyaluronic-acid-binding protein in the spleen, liver, macrophages, and serum of hamsters infected with this parasite (38).…”

Hyaluronan as an Immune Regulator in Human Diseases

“…Overexpression of HABP1 was seen during Leishmania donovani infection. HABP1 binds with 2 proteins of promastigotes as well as amastigotes of L. donovani , suggesting a possible role for HABP in adhesion during the interaction of promastigotes and macrophages (344). It is unknown whether HA is required in this interaction.…”

Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex

“…Our finding that L. chagasi promastigotes elicited a somewhat delayed response (peaking at 18 min) as compared to L. donovani (15 min) is intriguing, in view of the overall similarities of the activation profile of these species. The reasons for this difference in kinetics are not known, but could possibly be related to differential ability of these flagellates to move or migrate through the hyaluran-rich extracellular matrix of the HCP [34].…”

“…The reasons for the greater dependence of ACE inhibitor on L. donovani assays as opposed to those observed with L. chagasi are not known, but could relate to qualitative/quantitative differences in the expression of molecules that initiate inflammation by metacyclic versus stationary-phase promastigotes. As to the different kinetics observed with these two species, it is also possible that species specific differences in surface expression of hyaluran-binding proteins [34] may influence the parasite ability to move/migrate through the hyaluranrich extracellular matrix of the HCP.…”