Increase of RM3/1-positive macrophages in radiation-induced oral mucositis

Abstract

The purpose of this study was to describe the distribution patterns of various leukocyte subpopulations in the oral mucosa during the course of radiotherapy and to determine whether there are dose-dependent alterations, or any correlation between the clinical stages and the population density of specific leukocytes. The distribution and density of various leukocytes in oral mucosa in 13 head and neck cancer patients were immunohistochemically analysed before radiotherapy at 30 and 60 Gy and compared with the clinical degree of oral mucositis. Antibodies were used which characterized different subtypes of macrophages (27E10, 25F9, RM3/1) and recognized epitopes of granulocytes (CD15) and T cells (CD3, CD4, CD8). The study showed that whereas macrophages reactive with RM3/1 increased significantly at 30 Gy (p<0.01) and showed a further increase at 60 Gy (p<0.01), no significant alterations could be detected in the density of macrophages which stained positively for 27E10 or 25F9. Moreover, the percentage of macrophages reactive with RM3/1 showed a non-linear correlation with the clinical mucositis score (p<0.05). No significant alterations were detected in the percentage of T cells and granulocytes, compared with the values before radiotherapy. In conclusion, radiation-induced mucositis is characterized by features of an intermediate stage of an inflammatory response, suggesting active involvement of down-regulatory macrophages in its pathogenesis.

Histomorphometry and immunohistochemical features of grade I (WHO) oral radiomucositis

“…Interactions among mucosal cells, pro-inflammatory cytokines and local factors such as saliva and microorganisms probably play a key role (Pico et al, 1998;Sonis, 1998). The initial microscopic events seem to be increased submucosal vascularity and inflammatory cell infiltration, mainly macrophages (Sonis, 1998;Handschel et al, 2001b). Radiation causes cell lesion and liberation of cytokines from the epithelium and connective tissue, resulting in cell death and reduction of basal cell proliferation (Pico et al, 1998;Sonis, 1998).…”

“…Nevertheless, no previous study focused on Ki-67 epithelial labeling in oral mucositis, a reliable evaluation of proliferative reaction activity (Bruno and Darzynkiewicz, 1992). Indeed, only one study deals with macrophage subtypes during RxT and CD68 macrophage staining, which gives an overview, but including the relation with epithelium was never considered (Handschel et al, 2001b). The phenomenon of epithelial atypia was previously described induced by radiation, but no previous studies deal with it in oral mucositis, including p53 labeling, an important dysplastic biomarker (Kleebler and Somrak, 1993;Brien et al, 2001).…”

Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

“…In the normal human oral mucosa, macrophages are located mainly in the lamina propria (86) while PMNs appear in the lamina propria and epithelium only in response to inflammation (268). Macrophages are not a homogeneous cell population but can be separated into biologically active subpopulations which appear at early, intermediate, or late stages of inflammation (185).…”

Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis

“…This suggests that the reduction in myofibroblast number in the cheek pouch after SAP treatment is due to a mechanism upstream of direct modulation of fibroblast activity and may be due to modulation of monocyte differentiation. Future studies assessing the monocyte/macrophage phenotype in the cheek pouch should determine if there is also a profibrotic phenotype associated with the pathology observed in this model, as has been reported clinically [28]. Further, determining whether SAP can direct the macrophage phenotype away from a fibrotic M2 phenotype and towards a classic M1 macrophage phenotype will be insightful.…”