Angiotensin-Converting Enzyme, Transforming Growth Factor β1, and Interleukin 11 in the Osteolytic Lesions of Langerhans Cell Histiocytosis

Abstract

Abstract Objective.—To assess the expression of potential osteoclastogenic and osteolytic factors in osteolytic lesions from patients with Langerhans cell histiocytosis. Design.—Paraffin-embedded biopsy sections from 5 such archival cases underwent immunohistochemical procedures with antibodies to detect the following antigens: CD1a, S100 protein, interleukin 11, the latency-associated peptide of transforming growth factor β1, and angiotensin-converting enzyme. Results.—Commonalities noted include (1) the presence of multinucleated osteoclast-like giant cells, (2) the expression of interleukin 11 and latency-associated peptide antigens in lesional Langerhans cells, and (3) plasmalemmal immunoreactivity for angiotensin-converting enzyme antigen on non–Langerhans cell histiocytes and, on occasion, osteoclast-like giant cells and endothelial cells. Conclusions.—These observations suggest a possible pathogenetic sequence for osteolysis in Langerhans cell histiocytosis that involves angiotensin II formation, leading to the activation of latent transforming growth factor β1 and, in turn, to the enhanced production of interleukin 11, resulting in both osteoclastogenesis and impaired remodeling of bone.