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

Author(s)

Lorigados, Clara B. ^{[1, 2]} ; Ariga, Suely K. K. ^{[3, 4]} ; de Lima, Thais M. ^{[3, 4]} ; Barbeiro, Denise F. ^{[3, 4]} ; Krieger, Jose E. ^{[5, 6]} ; Soriano, Francisco G. ^{[3, 4]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Ortopedia & Traumatol, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Med Sch, Clin Hosp HCFMUSP, Trauma & Orthoped Inst, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med FMUSP, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Med Sch FMUSP, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Fac Med FMUSP, Inst Coracao, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Med Sch, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Shock; v. 51, n. 3, p. 381-388, MAR 2019.
• Web of Science Citations: 2

Abstract

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. (AU)

• FAPESP's process: 15/04138-2 - Sepsis and LPS tolerance - LPS tolerance role on oxidative stress and mithocondrial function, proteic nytrosilation and DNA damage
• Grantee: Francisco Garcia Soriano
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/03338-7 - Role of B-1 cell in the inflammatory response deflagrated by lipopolysacharide
• Grantee: Francisco Garcia Soriano
• Support Opportunities: Regular Research Grants