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 naive mice, these CRL+ cells, metallophilic macrophages (MO) in spleen and subcapsular sinus M(P 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+ Mphi. 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 Mphi in an immune response in vivo.