title: Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies.
abstract: The study of the murine macrophage mannose receptor (MR) has been hampered by the lack of specific reagents. We have generated and characterized novel anti-MR monoclonal antibodies and used them to analyze MR expression in primary mouse macrophages (M(phi)). In BioGel- and thioglycollate-elicited M(phi), interleukin (IL)-4 up-regulated total cell-associated MR (cMR), correlating with enhanced surface expression. We investigated the influence of IL-10, a well-characterized deactivator of M(phi) function, on MR levels and observed that it had a similar effect to IL-4. In both cases, enhanced cMR levels translated into increased production of the soluble form of the receptor (sMR). We have demonstrated the presence of sMR in cultures of stable non-M(phi) transductants expressing full-length MR, indicating that the proteolytic activity responsible for cMR cleavage is not M(phi)-restricted. These data support a role for the MR in T helper cell type 2 cytokine-driven, immune responses and suggest a non-M(phi) contribution to sMR production in vivo.
authors.affiliation: Sir William Dunn School of Pathology, Oxford, United Kingdom. Luisa.Martinez-Pomares@pathology.ox.ac.uk
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.forename: Delyth M
authors.initials: DM
authors.lastname: Reid
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stillion
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Linehan
authors.forename: Susanne
authors.initials: S
authors.lastname: Zamze
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin / Q000378:metabolism; D012995:Solubility; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; C023840:mannose-bovine serum albumin conjugate; D016753:Interleukin-10; D015847:Interleukin-4; D008358:Mannose