Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies

Luisa Martinez-Pomares; Delyth M Reid; Gordon D Brown; Philip R Taylor; Richard J Stillion; Sheena A Linehan; Susanne Zamze; Siamon Gordon; Simon Y C Wong

doi:10.1189/jlb.0902450

Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies

J Leukoc Biol. 2003 May;73(5):604-13. doi: 10.1189/jlb.0902450.

Authors

Luisa Martinez-Pomares¹, Delyth M Reid, Gordon D Brown, Philip R Taylor, Richard J Stillion, Sheena A Linehan, Susanne Zamze, Siamon Gordon, Simon Y C Wong

Affiliation

¹ Sir William Dunn School of Pathology, Oxford, United Kingdom. [email protected]

PMID: 12714575
DOI: 10.1189/jlb.0902450

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology*
Blotting, Western
CHO Cells
Cell Line
Cricetinae
Cricetulus
Endocytosis
Flow Cytometry
Interleukin-10 / pharmacology*
Interleukin-4 / pharmacology*
Lectins, C-Type / biosynthesis*
Lectins, C-Type / genetics
Lectins, C-Type / immunology
Macrophages, Peritoneal / drug effects*
Macrophages, Peritoneal / metabolism
Mannose / metabolism
Mannose Receptor
Mannose-Binding Lectins*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Receptors, Cell Surface / biosynthesis*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / immunology
Recombinant Fusion Proteins
Serum Albumin / metabolism
Solubility
Specific Pathogen-Free Organisms
Th2 Cells / immunology
Transduction, Genetic
Up-Regulation / drug effects

Substances

Antibodies, Monoclonal
Lectins, C-Type
Mannose Receptor
Mannose-Binding Lectins
Receptors, Cell Surface
Recombinant Fusion Proteins
Serum Albumin
mannose-bovine serum albumin conjugate
Interleukin-10
Interleukin-4
Mannose