title: Isolation and phenotypic characterization of a multinucleated tartrate-resistant acid phosphatase-positive bone marrow macrophage.
abstract: OBJECTIVE
  Prothrombin (PT) and osteopontin (OPN) promote adhesion of bone-derived tartrate-resistant acid phosphatase (TRAP, Acp5)-positive multinucleated cells differing in size, morphology, and resorptive activity. Here we explored phenotypic and functional differences between these cells.
  
  
  METHODS
  Global-wide and TRAP (Acp5) promoter messenger RNA expression, ability for phagocytosis, macrophage colony-stimulating factor-dependent migration, and in situ localization of these cells were investigated.
  
  
  RESULTS
  Gene expression of PT-adherent cells was skewed toward expression of innate immune response, phagocytosis, and scavenger receptor genes. They avidly phagocytosed Staphylococcus aureus and Dextran particles, and their migration on PT was enhanced by macrophage colony-stimulating factor. In contrast, OPN-adherent cells lacked ability to phagocytose particles and their migration on OPN was inhibited by macrophage colony-stimulating factor. They expressed typical osteoclast proteases implicated in bone matrix degradation, such as the collagenases cathepsin K; matrix metalloprotease-2; -9; -13; and -14, consistent with their high bone resorptive activity in vitro. In addition, OPN-adherent cells predominantly expressed the PU.1/MiTF/NFATc1-driven TRAP exon 1C messenger RNA, whereas PT-adherent cells preferably expressed TRAP exon 1B messenger RNA. Furthermore, CD163/cathepsin-K immunohistochemistry demonstrated that PT-adherent cells were predominantly located in the diaphyseal bone marrow compartment, whereas the OPN-adherent cells were attached to cortical and distal metaphyseal trabecular bone surfaces.
  
  
  CONCLUSIONS
  This study identifies differences in expression of several osteoclast and macrophage genes, as well as functional differences between PT- and OPN-adherent cells. We conclude that the OPN-adherent cells display osteoclast characteristics, especially with regard to expression of matrix-degrading enzymes, whereas the PT-adherent cell might represent a unique TRAP-positive multinucleated bone marrow macrophage implicated in immune recognition and phagocytosis.
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Karlström
authors.forename: Barbro
authors.initials: B
authors.lastname: Ek-Rylander
authors.forename: Mikael
authors.initials: M
authors.lastname: Wendel
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
mesh_terms: D000135:Acid Phosphatase / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002469:Cell Separation; D005786:Gene Expression Regulation / Q000502:physiology; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D009928:Organ Specificity / Q000502:physiology; D053495:Osteopontin / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D011516:Prothrombin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; C506897:Spp1 protein, rat; D053495:Osteopontin; D011516:Prothrombin; D000135:Acid Phosphatase; C000605512:Acp5 protein, rat; D000071681:Tartrate-Resistant Acid Phosphatase