ABSTRACT
BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.
Subject(s)
Antigens, CD1/radiation effects , Langerhans Cells/radiation effects , Macrophage-1 Antigen/radiation effects , Macrophages/radiation effects , Skin/radiation effects , Ultraviolet Rays , Adult , Analysis of Variance , Antigens, CD1/metabolism , Cell Count , Dose-Response Relationship, Radiation , Female , Humans , Immune Tolerance/radiation effects , Langerhans Cells/metabolism , Macrophage-1 Antigen/metabolism , Macrophages/metabolism , Male , Skin/metabolism , Sunburn/immunologyABSTRACT
PURPOSE: The purpose of our investigation was to describe the dose- and time-dependent histomorphologic alterations of the irradiated tissue, the composition of the infiltrate, and the expression patterns of various adhesion molecules. METHODS AND MATERIALS: We analyzed immunohistochemically alterations in oral mucosa in 13 head and neck cancer patients before radiotherapy and with 30 Gy and 60 Gy. All had oral mucosa irradiation, with a final dose of 60 Gy using conventional fractionation. Snap-frozen specimens were stained using the indirect immunperoxidase technique. Histomorphology was studied in paraffin-embedded sections. In addition, we determined the clinical degree of oral mucositis. RESULTS: Histomorphologic evaluation showed no vascular damage. Irradiation caused a steep increase of beta2-integrin-bearing cells (p < 0.01), whereas the percentage of beta1-integrin-positive cells remained at low levels. Additionally we found an increase in the expression of endothelial intercellular adhesion molecule-1 (ICAM-1) (p < 0.01) and E-selectin (p < 0.05), while endothelial vascular cell adhesion molecule-1 (VCAM-1) expression remained at very low levels. CONCLUSION: Our findings indicate that in radiation-induced oral mucositis there is no marked vascular damage until the end of radiotherapy. For recruitment of leukocytes, beta2 is more involved than beta1. Pharmaceuticals that block leukocyte adhesion to E-selectin or ICAM-1 may prevent radiation-mediated inflammation in oral mucosa.
Subject(s)
Cell Adhesion Molecules/radiation effects , Head and Neck Neoplasms/radiotherapy , Radiation Injuries/metabolism , Stomatitis/metabolism , Aged , Cell Adhesion Molecules/metabolism , Dose-Response Relationship, Radiation , E-Selectin/metabolism , E-Selectin/radiation effects , Humans , Integrin alpha4beta1 , Integrins/metabolism , Integrins/radiation effects , Intercellular Adhesion Molecule-1/metabolism , Intercellular Adhesion Molecule-1/radiation effects , Lymphocyte Function-Associated Antigen-1/metabolism , Lymphocyte Function-Associated Antigen-1/radiation effects , Macrophage-1 Antigen/metabolism , Macrophage-1 Antigen/radiation effects , Middle Aged , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , Mouth Mucosa/radiation effects , Prospective Studies , Radiation Injuries/pathology , Receptors, Lymphocyte Homing/metabolism , Receptors, Lymphocyte Homing/radiation effects , Stomatitis/etiology , Stomatitis/pathology , Time Factors , Vascular Cell Adhesion Molecule-1/metabolism , Vascular Cell Adhesion Molecule-1/radiation effectsABSTRACT
Dose-dependent damage to Fc and C3 receptors on leukocytes by ionizing radiation was obtained with monocytes in peripheral blood leukocytes (M-PBL) as well as granulocytes in bone marrow cells (G-BMC) from total body irradiated mice. G-BMC from these mice took more than 4 months after irradiation to present normal levels of Fc and C3 receptors. Evidence is provided that albumin can protect Fc and C3 receptors from the damage of ionizing radiation in a dose-dependent way, and that this radioprotection can last for several days after albumin administration. In general, M-PBL from cervical cancer patients under radiotherapy maintained normal values of C3 receptors as compared to non-albumin-treated patients where an important decrease was found.
