The Journal of Experimental Medicine
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Published 7 March 2005. doi:10.1084/jem.20041785
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 687-693
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BRIEF DEFINITIVE REPORT

 Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis

Cristiana E.T. da Costa1, Nicola E. Annels1, Claudia M.J.M. Faaij1, Ramses G. Forsyth3, Pancras C.W. Hogendoorn2, and R. Maarten Egeler1

1 Departments of Pediatric Immunology, Hematology, Oncology, Bone Marrow Transplantation, and Autoimmune Diseases
2 Department of Pathology, Leiden University Medical Centre, 2300 RC Leiden, Netherlands
3 N. Goormaghtigh Institute of Pathology, University Hospital Ghent, B-9000 Gent, Belgium

CORRESPONDENCE R. Maarten Egeler: rm.egeler{at}lumc.nl

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 {kappa}B 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.


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