Development of a specific system for targeting protein to metallophilic macrophages

Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1963-8. doi: 10.1073/pnas.0308490100. Epub 2004 Feb 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Complement Activation
  • Complement System Proteins / immunology
  • Cysteine / analysis
  • Cysteine / metabolism
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Lectins / metabolism
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Ligands
  • Luteinizing Hormone / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mannose Receptor
  • Mannose-Binding Lectins / chemistry
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Metals / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation / genetics
  • Protein Binding
  • Proteins / metabolism*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Substrate Specificity

Substances

  • Immunoglobulin Fc Fragments
  • Lectins
  • Lectins, C-Type
  • Ligands
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Metals
  • Proteins
  • Receptors, Cell Surface
  • Luteinizing Hormone
  • Complement System Proteins
  • Cysteine