Development of a specific system for targeting protein to metallophilic macrophages.
The cysteine-rich domain (CR) of the mannose receptor binds sulfated glycoprotein CR ligand (CRL) expressed by subpopulations of myeloid cells in secondary lymphoid organs (CRL(+) cells). In naïve mice, these CRL(+) cells, metallophilic macrophages (M) in spleen and subcapsular sinus M in lymph nodes, are located strategically for antigen capture and are adjacent to B cell follicles, but their role in the immune response is unknown. We have exploited the lectin activity of CR to develop a highly specific system for targeting protein to CRL(+) M. We demonstrate that the sulfated carbohydrates recognized by CR are exposed to the extracellular milieu and mediate highly specific targeting of CR-containing proteins. This model will allow the dissection of the role of metallophilic M in an immune response in vivo.
Taylor
Philip R
PR
Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford OX1 3RE, United Kingdom.
Zamze
Susanne
S
Stillion
Richard J
RJ
Wong
Simon Y C
SY
Gordon
Siamon
S
Martinez-Pomares
Luisa
L
D000818:Animals; D002417:Cattle; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology; D003545:Cysteine / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D007986:Luteinizing Hormone / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D007141:Immunoglobulin Fc Fragments; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008670:Metals; D011506:Proteins; D011956:Receptors, Cell Surface; D007986:Luteinizing Hormone; D003165:Complement System Proteins; D003545:Cysteine