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FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury

FTY720 (Fingolimod) is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues thereby causing peripheral lymphopenia. FTY720 can inhibit macrophage infiltration into inflammatory lesions under pathological conditions. FTY720 has been clinically evaluated...

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Detalles Bibliográficos
Autores principales: Zhang, Zhiyuan, Zhang, Zhiren, Fauser, Uwe, Artelt, Matthias, Burnet, Michael, Schluesener, Hermann J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822829/
https://www.ncbi.nlm.nih.gov/pubmed/17488479
http://dx.doi.org/10.1111/j.1582-4934.2007.00019.x
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author Zhang, Zhiyuan
Zhang, Zhiren
Fauser, Uwe
Artelt, Matthias
Burnet, Michael
Schluesener, Hermann J
author_facet Zhang, Zhiyuan
Zhang, Zhiren
Fauser, Uwe
Artelt, Matthias
Burnet, Michael
Schluesener, Hermann J
author_sort Zhang, Zhiyuan
collection PubMed
description FTY720 (Fingolimod) is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues thereby causing peripheral lymphopenia. FTY720 can inhibit macrophage infiltration into inflammatory lesions under pathological conditions. FTY720 has been clinically evaluated for prophylaxis of allograft rejection and treatment of multiple sclerosis, showing promising immunosuppressive effects. A robust inflammatory response after traumatic brain injury (TBI) plays an important role in the secondary or delayed injuries of TBI. Here we have investigated by immunohistochemistry in a rat TBI model the effects of FTY720 on early cell accumulation into the inflammatory tissue response and on expression of major histo-compatibility complex class II (MHC-II) and endothelial-monocyte activating polypeptide II (EMAP-II). Accumulation of MHC-II(+) or EMAP-II(+) cells became significant 1 day after injury and continuously increased during the early time periods. Further, double-staining experiments confirmed that the major cellular sources of MHC-II were reactive macrophages, however MHC-II(+) cells only constituted a small subpopulation of reactive macrophages. Immediately after TBI, peripheral administration of FTY720 (1 mg/kg in 1 mL saline, every second day) significantly attenuated the accumulation of MHC-II(+) macrophages from Day 1 to 4 and significantly attenuated the accumulation of EMAP-II(+) macrophages/microglia at Day 4. Our findings show that FTY720 attenuates early accumulation of EMAP-II(+) and MHC-II(+) reactive monocytes following TBI, indicating that FTY720 might be a drug candidate to inhibit brain inflammatory reaction following TBI.
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spelling pubmed-38228292015-04-27 FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury Zhang, Zhiyuan Zhang, Zhiren Fauser, Uwe Artelt, Matthias Burnet, Michael Schluesener, Hermann J J Cell Mol Med Articles FTY720 (Fingolimod) is a novel type of immunosuppressive agent inhibiting lymphocyte egress from secondary lymphoid tissues thereby causing peripheral lymphopenia. FTY720 can inhibit macrophage infiltration into inflammatory lesions under pathological conditions. FTY720 has been clinically evaluated for prophylaxis of allograft rejection and treatment of multiple sclerosis, showing promising immunosuppressive effects. A robust inflammatory response after traumatic brain injury (TBI) plays an important role in the secondary or delayed injuries of TBI. Here we have investigated by immunohistochemistry in a rat TBI model the effects of FTY720 on early cell accumulation into the inflammatory tissue response and on expression of major histo-compatibility complex class II (MHC-II) and endothelial-monocyte activating polypeptide II (EMAP-II). Accumulation of MHC-II(+) or EMAP-II(+) cells became significant 1 day after injury and continuously increased during the early time periods. Further, double-staining experiments confirmed that the major cellular sources of MHC-II were reactive macrophages, however MHC-II(+) cells only constituted a small subpopulation of reactive macrophages. Immediately after TBI, peripheral administration of FTY720 (1 mg/kg in 1 mL saline, every second day) significantly attenuated the accumulation of MHC-II(+) macrophages from Day 1 to 4 and significantly attenuated the accumulation of EMAP-II(+) macrophages/microglia at Day 4. Our findings show that FTY720 attenuates early accumulation of EMAP-II(+) and MHC-II(+) reactive monocytes following TBI, indicating that FTY720 might be a drug candidate to inhibit brain inflammatory reaction following TBI. Blackwell Publishing Ltd 2007-03 2007-05-01 /pmc/articles/PMC3822829/ /pubmed/17488479 http://dx.doi.org/10.1111/j.1582-4934.2007.00019.x Text en
spellingShingle Articles
Zhang, Zhiyuan
Zhang, Zhiren
Fauser, Uwe
Artelt, Matthias
Burnet, Michael
Schluesener, Hermann J
FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title_full FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title_fullStr FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title_full_unstemmed FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title_short FTY720 attenuates accumulation of EMAP-II(+) and MHC-II(+) monocytes in early lesions of rat traumatic brain injury
title_sort fty720 attenuates accumulation of emap-ii(+) and mhc-ii(+) monocytes in early lesions of rat traumatic brain injury
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822829/
https://www.ncbi.nlm.nih.gov/pubmed/17488479
http://dx.doi.org/10.1111/j.1582-4934.2007.00019.x
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