HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kedzierski, L. Articles by Handman, E. Search for Related Content PubMed PubMed Citation Articles by Kedzierski, L. Articles by Handman, E.

A Leucine-Rich Repeat Motif of Leishmania Parasite Surface Antigen 2 Binds to Macrophages through the Complement Receptor 3¹

Lukasz Kedzierski^*, Jacqui Montgomery^*, Denise Bullen^*, Joan Curtis^*, Elizabeth Gardiner, Antonio Jimenez-Ruiz and Emanuela Handman^2,*

^* Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia; and Department of Biochemistry and Molecular Biology, University of Alcalá, Madrid, Spain

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.

This article has been cited by other articles:

				B. Lu and M. PereiraPerrin A Novel Immunoprecipitation Strategy Identifies a Unique Functional Mimic of the Glial Cell Line-Derived Neurotrophic Factor Family Ligands in the Pathogen Trypanosoma cruzi Infect. Immun., August 1, 2008; 76(8): 3530 - 3538. [Abstract] [Full Text] [PDF]

				C. Zhao, S. Thibault, N. Messier, M. Ouellette, B. Papadopoulou, and M. J. Tremblay In primary human monocyte-derived macrophages exposed to Human immunodeficiency virus type 1, does the increased intracellular growth of Leishmania infantum rely on its enhanced uptake? J. Gen. Virol., May 1, 2006; 87(Pt 5): 1295 - 1302. [Abstract] [Full Text] [PDF]

				R. C. Hespanhol, M. de Nazare C. Soeiro, M. B. Meuser, M. de Nazareth S.L. Meirelles, and S. Corte-Real The Expression of Mannose Receptors in Skin Fibroblast and Their Involvement in Leishmania (L.) amazonensis Invasion J. Histochem. Cytochem., January 1, 2005; 53(1): 35 - 44. [Abstract] [Full Text] [PDF]

				D. R. Greaves and S. Gordon Thematic review series: The Immune System and Atherogenesis. Recent insights into the biology of macrophage scavenger receptors J. Lipid Res., January 1, 2005; 46(1): 11 - 20. [Abstract] [Full Text] [PDF]