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Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose.

ABSTRACT: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5?Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of hTNF-? tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0?Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5?Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions.

SUBMITTER: Deloch L

PROVIDER: S-EPMC6710796 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose.

Deloch Lisa L Fuchs Jana J Rückert Michael M Fietkau Rainer R Frey Benjamin B Gaipl Udo S US

Journal of immunology research 20190814

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain ...[more]

PMID: 31485459

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Project description:The local Fourier-space relation between diffracted intensity I, diffraction wavevector q and dose D, , is key to probing and understanding radiation damage by X-rays and energetic particles in both diffraction and imaging experiments. The models used in protein crystallography for the last 50 years provide good fits to experimental I(q) versus nominal dose data, but have unclear physical significance. More recently, a fit to diffraction and imaging experiments suggested that the maximum tolerable dose varies as q -1 or linearly with resolution. Here, it is shown that crystallographic data have been strongly perturbed by the effects of spatially nonuniform crystal irradiation and diffraction during data collection. Reanalysis shows that these data are consistent with a purely exponential local dose dependence, = I 0(q)exp[-D/D e(q)], where D e(q) ? q ? with ? ? 1.7. A physics-based model for radiation damage, in which damage events occurring at random locations within a sample each cause energy deposition and blurring of the electron density within a small volume, predicts this exponential variation with dose for all q values and a decay exponent ? ? 2 in two and three dimensions, roughly consistent with both diffraction and imaging experiments over more than two orders of magnitude in resolution. The B-factor model used to account for radiation damage in crystallographic scaling programs is consistent with ? = 2, but may not accurately capture the dose dependencies of structure factors under typical nonuniform illumination conditions. The strong q dependence of radiation-induced diffraction decays implies that the previously proposed 20-30?MGy dose limit for protein crystallography should be replaced by a resolution-dependent dose limit that, for atomic resolution data sets, will be much smaller. The results suggest that the physics underlying basic experimental trends in radiation damage at T ? 100?K is straightforward and universal. Deviations of the local I(q, D) from strictly exponential behavior may provide mechanistic insights, especially into the radiation-damage processes responsible for the greatly increased radiation sensitivity observed at T ? 300?K.

Dataset Information

Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose.

Publications

Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose.

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