Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis

Background Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. the aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction.Methods A total of 41 patients were prospectively enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. A total of 17 healthy volunteers were included as a control group. Patients were admitted to the Intensive Care Units and Emergency Rooms of Hospital São Paulo ( Federal University of São Paulo) and Hospital Santa Marcelina, São Paulo, Brazil. Toll- like receptor ( TLR) 2, TLR4, CD11b, CD11c and CD66b expression on neutrophil surfaces and oxidative metabolism measured by non- fluorescent dichlorofluorescein ( DCFH) oxidation in neutrophils and monocytes, using whole blood, were evaluated using flow cytometry. Organ dysfunction was measured using the sepsis- associated organ failure assessment ( SOFA) score.Results TLR2 expression on neutrophils was found to be downregulated in septic shock patients compared to healthy volunteers ( p = 0.05). No differences were found in CD11b and CD11c expression. CD66b expression was increased in the patient group compared to the control group ( p = 0.01). Neutrophil and monocyte oxidative burst was increased in septic patients compared to the control group at baseline and after stimulation with phorbol myristate acetate ( PMA), formylmethionylleucyl- phenylalanine ( fMLP), lipopolysaccharide ( LPS) and Staphylococcus aureus ( p 7 was higher than in patients with SOFA scores < 7, both in neutrophils and monocytes. However, oxidative burst in patients with sepsis was as high as in septic shock.Conclusion Surface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered. ROS generation is upregulated both in neutrophils and monocytes in septic patients, and it is differently modulated depending on the stage of the disease and the stimuli used.Universidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Intens Care Unit, São Paulo, BrazilHosp St Marcelina, Intens Care Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Intens Care Unit, São Paulo, BrazilWeb of Scienc

The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

<p>Abstract</p> <p>Background</p> <p>CD4⁺CD25^highregulatory T (T_Reg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T_Regcell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T_Regcells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation.</p> <p>Results</p> <p>We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4⁺T_Regcells (CD4⁺CD25^highT cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4⁺T_Regcells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127^lowT_Regcells in healthy control subjects. Finally, the proportion of CD127^lowT_Regcells correlated inversely with HTLV-1 proviral load.</p> <p>Conclusion</p> <p>Taken together, the results suggest that T_Regcells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4⁺T cells, in particular those expressing the CD25^highCD127^lowphenotype. T_Regcells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.</p

PROTEOMIC STUDY REVEALED DYSREGULATION OF CYTOSKELETON AND LIPID METABOLISM IN SEPTIC PATIENTS SECONDARY TO COMMUNITY ACQUIRED PNEUMONIA

Univ Fed Sao Paulo, Hosp Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilHosp Israelita Albert Einstein, Sao Paulo, BrazilHosp Sirio Libanes, Sao Paulo, BrazilUniv Fed Sao Paulo, Hosp Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Neutrophil reactive oxygen species (ROS) generation in patients across the continuum of sepsis

ROS generation was measured by 2',7'dichlorofluorescein (DCFH) metabolism. Neutrophils were gated based on FSC versus SSC parameters and the expression of CD14 on cell surface. ROS generation was analyzed in histograms and expressed as the geometric mean fluorescence intensity (GMFI). *p < 0.01 compared to healthy volunteers; #p < 0.05 compared to the severe sepsis group; §p < 0.05 compared to the septic shock group.<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Correlation between formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species (ROS) generation and sepsis-associated organ failure assessment (SOFA) score in neutrophils and monocytes in patients with severe sepsis and septic shock

<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Correlation between neutrophil and monocyte oxidative metabolism in septic patients at baseline (A) and after stimuli with phorbol myristate acetate (PMA) (B), formyl-methionyl-leucyl-phenylalanine (fMLP) (C), lipopolysaccharide (LPS) (D) and (E)

<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Dot plots depict the gating strategies for CD25and CD25cells (A); CD127(B); and CTLA-4 expression (C) are shown

The gates for CD25and CD4CD25T cells were set based on the expression level of CD25 on CD4T cells, where the pattern of CD25 expression is more distinct. Accordingly, CD4CD25T cells were defined as those expressing CD25 at a level higher than the bulk CD4CD25population. For D-K, individual results are represented in symbols, and the line represents the mean. (D) % CD4CD25T cells; (E) % CD4CD25T cells; (F) % CD4CD25CTLA-4T cells; (G) % of CD4CD25CTLA-4T cells; (H) % CD4CD25CD127T cells; (I) % CD4CD25CD127T cells; (J) % CD4CD25GITRT cells; and (K) % CD4CD25GITRT cells.<p><b>Copyright information:</b></p><p>Taken from "The frequency of CD127expressing CD4CD25T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis"</p><p>http://www.biomedcentral.com/1471-2172/9/41</p><p>BMC Immunology 2008;9():41-41.</p><p>Published online 29 Jul 2008</p><p>PMCID:PMC2515103.</p><p></p