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 of Plasmodium falciparum-infected erythrocytes (PE) to immobilized chondroitin sulfate A (CSA)-conjugated albumin at a concentration of 100 microg/mL and blocked the PE binding to CD36-expressing Chinese hamster ovary (CHO) cells, as well as immobilized CD36 at concentrations of 5 microg/mL and 100 microg/mL, respectively. Biotinylated LF bound to CD36 in a saturable manner, and such binding was inhibited by unlabeled LF and the anti-CD36 monoclonal antibody, 8A6, suggesting specificity of binding. Additionally, LF inhibited PE binding to immobilized thrombospondin (TSP) at a concentration of 100 microg/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-dependent 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 contribute to LF binding to various materials, including CSA, inhibited PE binding to immobilized CSA-conjugated albumin, immobilized CD36, CD36-expressing CHO cells, immobilized TSP, and C32 amelanotic melanoma cells, as well as LF itself. These results suggest that LF peptide may provide the basis for developing agents that are able to inhibit CSA-, CD36-, and TSP-mediated cytoadherence of PE.
Eda
S
S
Department of Biology, University of California, Riverside, CA 92521, USA.
Eda
K
K
Prudhomme
J G
JG
Sherman
I W
IW
D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis / Q000494:pharmacology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D006224:Cricetinae; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D006801:Humans; D007781:Lactoferrin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000097:blood / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D010963:Plasmodium falciparum; D019699:Thrombospondins / Q000494:pharmacology*
D018955:CD36 Antigens; D010446:Peptide Fragments; D019699:Thrombospondins; D002809:Chondroitin Sulfates; D007781:Lactoferrin