Miklos, Sandra and Mueller, Gunnar and Chang, Yayi and Bouazzaoui, Abdellatif and Spacenko, Elena and Schubert, Thomas E. O. and Grainger, David J. and Holler, Ernst and Andreesen, Reinhard and Hildebrandt, Gerhard C. (2009) Preventive usage of broad spectrum chemokine inhibitor NR58-3.14.3 reduces the severity of pulmonary and hepatic graft-versus-host disease. INTERNATIONAL JOURNAL OF HEMATOLOGY, 89 (3). pp. 383-397. ISSN 0925-5710, 1865-3774
Full text not available from this repository. (Request a copy)Abstract
Pulmonary graft-versus-host disease (pGVHD) is a major complication after allogeneic bone marrow transplantation (BMT), which involves donor leukocyte migration into the lung along chemokine gradients, leading to pulmonary dysfunction and respiratory insufficiency. As broad spectrum chemokine inhibitor (BSCI) NR58-3.14.3 suppresses leukocyte migration in response to various chemokines, including CCL2, CCL3, CCL5, we investigated the effects of NR58-3.14.3 on the evolution of pGVHD. Lethally irradiated B6D2F1 mice received BMT from syngeneic (B6D2F1) or allogeneic (C57BL/6) donors, and animals were treated with either NR58-3.14.3 or vehicle control from day -1 to day +14. At week 6, in allogeneic recipients that received BSCI, inflammatory cell infiltrates in the lung were decreased, and reduced histopathologic changes translated into improved pulmonary function when compared to allo-controls. Acute GVHD of the liver was also diminished, whereas no differences were seen in the gut. Alloantigen-dependent splenic T cell expansion and systemic TNF-alpha and IFN-gamma levels were comparable in NR58-3.14.3-treated animals and allo-controls. No suppressive effect of NR58-3.14.3 on CTL cytotoxicity was found, and diminished cellular infiltrates in lung and liver were most likely due to decreased migration of mononuclear cells. Therefore, novel approaches involving BSCIs may provide a promising tool in the management of pGVHD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IDIOPATHIC PNEUMONIA SYNDROME; BONE-MARROW-TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; STEM-CELL TRANSPLANTATION; INTERCELLULAR-ADHESION MOLECULE-1; EARLY PROINFLAMMATORY EVENTS; ISCHEMIA-REPERFUSION INJURY; DONOR T-CELLS; LUNG INJURY; LEUKOCYTE RECRUITMENT; Lung; Allogeneic bone marrow transplantation; Chemokine; Graft-versus-host disease; Idiopathic pneumonia syndrome |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Sep 2020 09:11 |
| Last Modified: | 18 Sep 2020 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29170 |
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