Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis.
Langerhans cell histiocytosis (LCH) is a disease that can involve one or multiple organ systems characterized by an accumulation of CD1a(+) Langerhans-like cells as well as several other myeloid cell types. The precise origin and role of one of these populations, the multinucleated giant cell (MGC), in this disease remains unknown. This work shows that in three different lesional tissues, bone, skin, and lymph node, the MGCs expressed the characteristic osteoclast markers, tartrate-resistant acid phosphatase and vitronectin receptor, as well as the enzymes cathepsin K and matrix metalloproteinase-9. Although, in bone lesions, the osteoclast-like MGCs were only CD68(+), in the nonostotic sites, they coexpressed CD1a. The presence of osteoclast-like MGCs may be explained by the production of osteoclast-inducing cytokines such as receptor activator of nuclear factor kappaB ligand and macrophage colony-stimulating factor by both the CD1a(+) LCH cells and T cells in these lesions. As osteoclast-derived enzymes play a major role in tissue destruction, the osteoclast-like nature of MGCs in all LCH lesions makes them a potential target for the treatment of this disease.
da Costa
Cristiana E T
CE
Department of Pediatric Immunology, Leiden University Medical Centre, 2300 RC Leiden, Netherlands.
Annels
Nicola E
NE
Faaij
Claudia M J M
CM
Forsyth
Ramses G
RG
Hogendoorn
Pancras C W
PC
Egeler
R Maarten
RM
D015415:Biomarkers / Q000032:analysis; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology*; D006646:Histiocytosis, Langerhans-Cell / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D063065:Organophosphonates / Q000627:therapeutic use; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D063065:Organophosphonates; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor