title: Receptor usage by the Acanthocheilonema viteae-derived immunomodulator, ES-62.
abstract: ES-62 is an immunomodulatory phosphorylcholine (PC)-containing glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae. Previously, the use of knockout mice has revealed the effects of ES-62 on macrophages and dendritic cells to be dependent on TLR4. However, it is possible that ES-62 may interact with additional proteins on the surfaces of target cells and hence that cells may vary with respect to receptor usage. In this study, we identified by molecular weight, proteins that interact with ES-62 and found differences amongst the immune system cells studied. Thus, whereas lymphocytes appear to have two major interacting proteins of ∼135 and ∼82 kDa, U937 monocytes only contain an ES-62-binding protein of the latter molecular weight. Binding to the proteins on B cells and U937 cells was blocked by PC, suggesting a critical role for this ES-62 moiety in facilitating interaction. Finally, ES-62 binding is followed by internalization in both macrophages and B cells but only in the former was absence of TLR4 found to block internalization. These findings are consistent with differences in receptor usage by ES-62 amongst different cell-types.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. w.harnett@strath.ac.uk
authors.forename: William
authors.initials: W
authors.lastname: Harnett
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.forename: Margaret
authors.initials: M
authors.lastname: Harnett
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015374:Biosensing Techniques; D015153:Blotting, Western; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004153:Dipetalonema / Q000276:immunology / Q000378:metabolism*; D015801:Helminth Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000737:chemistry / Q000378:metabolism*; D020298:U937 Cells
chemical_list: C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4