BONE MARROW CELLS TRANSPLANT IN SEPTIC MICE MODULATES SYSTEMIC INFLAMMATORY RESPONSE VIA CELL-CELL CONTACT

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Citações na Scopus
5
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Citação
SHOCK, v.51, n.3, p.381-388, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Sepsis is a dynamic disease, displaying an inflammatory profile that varies over time and for each organ. Controlling the inflammatory response based in targeting a single molecule has been proved useless. We hypothesized that treatment with bone marrow-derived mononuclear cells (BMDMCs) may be more efficient to modulate the systemic inflammatory response to infection. Adult male Balb/c mice were subjected to cecal ligation and puncture (CLP) or endotoxemia model of experimental sepsis. BMDMCs were separated under Ficoll gradient and injected intravenously 1 h after the procedures. Cytokines concentration was quantified in plasma, lungs, heart, and gut. Spleens, lymph nodes, and thymus were used for lymphocytes isolation and cell death assessment. All measurements were performed 2 h after BMDMCs injection. RAW264.7 macrophages and BMDMCs were cocultivated in vitro to investigate the mechanisms involved. Our data showed that an early single intravenous injection of BMDMCs in animals submitted to the murine model of endotoxemia led to the improvement of survival rate; BMDMCs persistency in lung, liver, and spleen after 24 h; decreased necrosis and apoptosis of mononuclear cells; lower TNF-a, but increased IL-10 concentration in plasma; and tissue-specific cytokine profile. In vitro experiments demonstrated that IL-6, IL-10, and nitric oxide production depends on direct contact of BMDMCs to macrophages and that TNF-a production is negatively regulated by PGE2. BMDMCs are efficient in protecting animals from endotoxemia and sepsis, reducing systemic inflammation as well as specifically modulating tissue inflammation, producing the necessary immune regulation to re-equilibrate the inflammatory response.
Palavras-chave
Bone marrow-derived mononuclear cells, cell-to-cell contact, cytokine, endotoxemia, inflammation, sepsis
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