title: Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype: their possible involvement in pathological processes.
abstract: Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Iyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015726:Giant Cells / Q000276:immunology / Q000473:pathology; D006646:Histiocytosis, Langerhans-Cell / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D055672:Static Electricity; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; D016753:Interleukin-10