Bertulat, B.

Cardoso, M. C.

Dettmering, T.

Durante, M.

Erbeldinger, N.

Fournier, C.

Meyer, S.

Rödel, F.

Zimmermann, J.

GSI Repository

Insights in the molecular basis of a reduced lymphocyte adhesion to irradiatedand stimulated primary endothelial cells ∗N. Erbeldinger1, S. Meyer2, J. Zimmermann1, T. Dettmering1, B. Bertulat2, M. Durante1,2, F. Ro¨del3,M.C. Cardoso2, and C. Fournier11GSI, Darmstadt, Germany; 2Technische Universita¨t Darmstadt, Darmstadt, Germany; 3Universita¨tsklinikum Frankfurt,GermanyWe reported previously a radiation induced loweredadhesion of immune cells on hybrid endothelial cells(EA.hy.926) as a model of the inner layer of the blood ves-sel walls [1], which is one possible modification of inflam-matory processes in the treatment of chronic inflammatorydiseases [2]. Recently, we could further show a relation-ship between metabolic ROS accumulation and modifica-tion of adhesion at low doses in the EA.hy.926 endothelialcell line [3]. We now measured the adhesion of immunecells to primary endothelial cells and assessed NFκB nu-clear translocation as a putative molecular basis implicatedin the lowered adhesion.X-ray irradiation (250 kV, 16 mA) of primary endothe-lial cells (HMVEC) and adhesion assay to TNF-α treatedHMVEC was performed with isolated peripheral bloodlymphocytes (PBL) according to [1]. TNF-α inducedNFκB signalling was analysed in parallel by quantificationof the nuclear p65 translocation. Figure 1 shows that theadhesion of non-irradiated PBLs to HMVEC is enhancedby inflammatory TNF-α treatment, whereas the adhesionis reduced in the low dose range (0.1−0.5 Gy) 24h afterX-ray exposure. In the presence of TNF-α, non-irradiatedEC show nuclear translocation of p65 (not shown), but ir-radiation did not modify this (Figure 2).Figure 1: X-ray induced reduced adhesion of PBL tostimulated HMVEC under static conditions normalized tonon-irradiated HMVEC. The response for non-stimulatedHMVEC is shown as a comparison.∗Financed by by BMBF (GREWIS, 02NUK017A, 02NUK017F,02NUK017D), DFG (GRK 1657), FOI Bad Gastein.0 h 1 h 1 h 1 h00.51.512X-rayprimary endothelial cells (HMVEC)relative nucleus intensitycontrolTNFalpha0 Gy0.5 Gy6 GyFigure 2: Activation of NFκB signalling via nucleartranslocation of p65 in TNF-α stimulated HMVEC 1h af-ter X-ray exposure, normalized to stimulated and non-irradiated HMVEC.These results confirm that low dose X-ray exposure ofprimary EC reduces the adhesion of PBL to EC, but ratherbased on ROS accumulation than on modification of NFκBnuclear translocation.References[1] Erbeldinger et al., GSI annual report, 2013[2] Ro¨del et al. (2007), IJRB83(6): 357-366.[3] Large et al. Radiat Oncol (2014), 9:80GSI SCIENTIFIC REPORT 2014 APPA-HEALTH-09DOI:10.15120/GR-2015-1-APPA-HEALTH-09 299

Insights in the molecular basis of a reduced lymphocyte adhesion to irradiated and stimulated primary endothelial cells

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Insights in the molecular basis of a reduced lymphocyte adhesion to irradiated and stimulated primary endothelial cells

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