Inhibitory activity of human lactoferrin and its peptide on chondroitin sulfate A-, CD36-, and thrombospondin-mediated cytoadherence of Plasmodium falciparum-infected erythrocytes

Lactoferrin (LF), a human serum protein, strongly inhibited the adherence o f Plasmodium falciparum-infected erythrocytes (PE) to immobilized chondroit in sulfate A (CSA)conjugated albumin at a concentration of 100 mu g/mL and blocked the PE binding to CD36-expressing Chinese hamster ovary (CHO) cells , as well as immobilized CD36 at concentrations of 5 mu g/mL and 100 mu g/m L, respectively. Biotinylated LF bound to CD36 in a saturable manner, and s uch binding was inhibited by unlabeled LF and the anti-CD36 monoclonal anti body, 8A6, suggesting specificity of binding. Additionally, LF inhibited PE binding to immobilized thrombospondin (TSP) at a concentration of 100 mu g /mL, and specific binding of LF to TSP was confirmed using biotinylated LF. LF inhibited PE binding to C32 amelanotic melanoma cells in a dose-depende nt manner. A peptide of LF, Arg-Asn-Met Arg-Lys-Val Arg Gly-Pro-Pro-Val-Ser -Cys (amino acid residues 25-37 of LF), which has been suggested to contrib ute to LF binding to various materials, including CSA, inhibited PE binding to immobilized CSA conjugated albumin, immobilized CD36, CD36-expressing C HO cells, immobilized TSP, and C32 amelanotic melanoma cells, as well as LF itself. These results suggest that LF peptide may provide the basis for de veloping agents that are able to inhibit CSA-, CD36-, and TSP-mediated cyto adherence of PE. (C) 1999 by The American Society of Hematology.