Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies.
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.
Martinez-Pomares
Luisa
L
Sir William Dunn School of Pathology, Oxford, United Kingdom. Luisa.Martinez-Pomares@pathology.ox.ac.uk
Reid
Delyth M
DM
Brown
Gordon D
GD
Taylor
Philip R
PR
Stillion
Richard J
RJ
Linehan
Sheena A
SA
Zamze
Susanne
S
Gordon
Siamon
S
Wong
Simon Y C
SY
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
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