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G-CSF–treated granulocytes inhibit acute graft-versus-host disease

Vasconcelos, Zilton F. M. ; Santos, Bruna M. dos ; Farache, Julia ; Palmeira, Tereza S. S. ; Areal, R“mulo B. ; Cunha, Jos‚ Marcos T. ; Barcinski, Marcello A. ; Bonomo, Adriana.
Blood ; 107(5): 2192-2199, mar. 2006. ilus, graf
Artículo en Inglés | TXTC | ID: txt-22257
It has been shown that in vivo and in vitrotreatment with G-CSF induces the generationof low-density granulocytes (LDGs),which copurify with PBMCs and inhibitIFN- production by human T cells. Theseresults prompted us to postulate an immunomodulatoryrole for LDGs in acute graftversus-host disease (aGVHD). Here it isshown that in the mouse experimentalmodel, in vivo and in vitro G-CSF treatmentgenerates LDGs capable of inhibiting80% of T-cell IFN- production. Toassess the role of these LDGs in aGVHD,lethally irradiated (C57BL/6 BALB/c) F1hosts were reconstituted with T cell–depleted bone marrow cells plus nylonwool–purified spleen cells from G-CSF–treated (G-NWS) or –nontreated (NWS)C57BL/6 donors. Recipients of G-NWShad a 75% survival rate in contrast to arate of 25% in the NWS recipients. Theprotective effect was completely abolished,and the mortality rate was 100% ifdonor-cell infusion was treated with anti-Gr1. Moreover, if LDGs were infused withNWS, full protection of aGVHD was observed,and no signs of disease wereevidenced by mortality rate, weight loss,or histopathology of target organs. Theseresults revealed the unexpected immunosuppressivecapacity of G-CSF based onthe generation of LDGs, leading to thepossibility of using these cells as inhibitorsof aGVHD.
Biblioteca responsable: BR440.1
Ubicación: BR440.1