title: A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3.
abstract: Membrane glycoconjugates on the Leishmania parasites, notably leishmanolysin and lipophosphoglycan, have been implicated in attachment and invasion of host macrophages. However, the function of parasite surface Ag 2 (PSA-2) and membrane proteophosphoglycan (PPG) has not been elucidated. In this study we demonstrate that native and recombinant Leishmania infantum PSA-2, which consists predominantly of 15 leucine-rich repeats (LRR) and a recombinant LRR domain derived from L. major PPG, bind to macrophages. The interaction is restricted to macrophages and appears to be calcium independent. We have investigated the PSA-2-macrophage interaction to identify the host receptor involved in binding and we show that binding of PSA-2 to macrophages can be blocked by Abs to the complement receptor 3 (CR3, Mac-1). Data derived from mouse macrophage studies were further confirmed using cell lines expressing human CR3, and showed that PSA-2 also binds to the human receptor. This is the first demonstration of a functional role for PSA-2. Our data indicate that in addition to leishmanolysin and lipophosphoglycan, parasite attachment and invasion of macrophages involve a third ligand comprising the LRRs shared by PSA-2 and PPG and that these interactions occur via the CR3.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.forename: Jacqui
authors.initials: J
authors.lastname: Montgomery
authors.forename: Denise
authors.initials: D
authors.lastname: Bullen
authors.forename: Joan
authors.initials: J
authors.lastname: Curtis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gardiner
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimenez-Ruiz
authors.forename: Emanuela
authors.initials: E
authors.lastname: Handman
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D018314:Leishmania infantum / Q000276:immunology*; D007930:Leucine / Q000378:metabolism*; D000090263:Leucine-Rich Repeat Proteins; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000090263:Leucine-Rich Repeat Proteins; D016177:Macrophage-1 Antigen; D011506:Proteins; D015800:Protozoan Proteins; C072094:surface antigen P2, Leishmania; D007930:Leucine