Functional analysis of monocyte MHC class II compartments

Allyson Bunbury, Ilaria Potolicchio, Radhashree Maitra, Laura Santambrogio

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Circulating monocytes, as dendritic cell and macrophage precursors, exhibit several functions usually associated with antigen-presenting cells, such as phagocytosis and presence of endosomal/lysosomal degradative compartments particularly enriched in Lamp-1, MHC class II molecules, and other proteins related to antigen processing and MHC class II loading [MHC class II compartments (MIICs)]. Ultrastructural analysis of these organelles indicates that, differently from the multivesicular bodies present in dendritic cells, in monocytes the MIICs are characterized by a single perimetral membrane surrounding an electron-dense core. Analysis of their content reveals enrichment in myeloperoxidase, an enzyme classically associated with azurophilic granules in granulocytes and mast cell secretory lysosomes. Elevation in intracellular free calcium levels in monocytes induced secretion of β-hexosaminidase, cathepsins, and myeloperoxidase in the extracellular milieu; surface up-regulation of MHC class II molecules; and appearance of lysosomal resident proteins. The Ca2+-regulated surface transport mechanism of MHC class II molecules observed in monocytes is different from the tubulovesicular organization of the multivesicular bodies previously reported in dendritic cells and macrophages. Hence, in monocytes, MHC class II-enriched organelles combine degradative functions typical of lysosomes and regulated secretion typical of secretory lysosomes. More important, Ca2+-mediated up-regulation of surface MHC class II molecules is accompanied by extracellular release of lysosomal resident enzymes.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalFASEB Journal
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Calcium flux
  • Cathepsins
  • Lysosomes
  • MHCII trafficking
  • MIIC

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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