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,
, Results in A-D show values from individual mice; bars indicate means ± SEM pooled from two independent experiments (total n = 4-5/ group). *, P < 0.05 versus control 0 group by two-tailed Mann-Whitney U test. (E and F) Percentage of Gr-1 high CD11b + blood neutrophils at the indicated time point after injection of 25 mg/kg LPS in C57BL/6J mice treated i.p. with an anti-Ly6G neutrophil-depleting antibody, Phenotype of neutrophils in the peritoneum and BM after LPS injection, and effect of treatment with neutrophil-depleting antibodies in models of LPS-or LPS/d-galactosamine-induced endotoxemia
, in C57BL/6J mice treated i.p. with an anti-Gr-1 neutrophil-depleting antibody (clone RB6-8C5; 300 µg/ injection) or an isotype control antibody
, Data in E and F are pooled from three independent experiments
, 001 versus the corresponding isotype control group by two-tailed Mann-Whitney U test. (G-J) Changes in body temperature
, Data in G-J are pooled from two or three independent experiments (total n = 8-12/group). ***, P < 0.001 versus the corresponding isotype control group by Mantel-Cox log-rank test. Arrows in G-J indicate time of i.p. injection of the neutrophil-depleting or isotype control antibodies. S13 JEM Figure S2. Analysis of GFP expression in various immune cell types from MRP8-Cre/IRES-GFP mice, levels of various cell populations 24 h after DT injection into PMN DTR mice, and responses of PMN DTR mice in the CLP model of polymicrobial sepsis. (A) Analysis of GFP expression (mean fluorescence intensity) in the indicated cell populations in MRP8-Cre/IRES-GFP ? and MRP8-Cre/IRES-GFP + mice. Results are representative of three independent experiments. (B) Analysis of YFP expression in myeloid leukocytes from the blood of MRP8-Cre/IRES-GFP + × ROSA-iEYFP KI reporter mice, graphed as percentage YFP + of the indicated populations. Values from individual mice are shown; bars indicate means pooled from two independent experiments (total n = 7). Neut, neutrophils; Eosin, eosinophils. (C) Percentage of blood, spleen, and BM neutrophils 24 h after i.p. injection of 500 ng DT into PMN DTR mice and PMN WT littermate control mice. (D) Percentage of blood neutrophils at the indicated time points after i.p. injection of DT on day 0. Results in D are means ± SEM from n = 3-8 mice per group pooled from two or three independent experiments. (E-H) Numbers of various cell populations in blood (E), spleen (F), peritoneal lavage fluid (G), and BM (H) from PMN DTR mice and PMN WT littermate control mice 24 h after i.p. injection of 500 ng DT, percentage of live animals; I and J) after injection of 2.5 mg/kg LPS (G and I) or 10 µg/kg LPS together with the indicated concentration of d-galactosamine (Galn; H and J) in C57BL/6J mice treated i.p. with an anti-Gr-1 neutrophil-depleting antibody (clone RB6-8C5; 300 µg/ injection) or an isotype control antibody (rat IgG2b)
, Ly6C low ; total n = 8-10/group) and BM B cells (total n = 5/group), four experiments for blood neutrophils (B; total n = 15-16/group), or three independent experiments for all other cell populations (total n = 7-15/group)
,
, Survival after CLP (n = 12-16). (J-L) Numbers of bacterial CFUs in the blood (J) and peritoneal lavage fluid (K) and numbers of blood and peritoneal neutrophils (L) 18 h after CLP (n = 8-13/group). (M) Levels of TNF-?, IL-6, MCP-1, and IL-12 in the plasma 18 h after CLP (n = 7-8/group). Results in J-L show values from individual mice; bars indicate means ± SEM, M?, macrophages. (I-M) Responses of DT-treated PMN DTR versus PMN WT mice in the CLP model of polymicrobial sepsis. (I)
,
, Arrows in D and I indicate days of i.p. injection of the neutrophil-depleting or isotype control antibodies. Neutrophil MPO protects against
, A-E) Responses of Mpo ?/? versus WT mice in the CLP model of polymicrobial sepsis. (A) Survival after CLP (n = 12). (B-E) Numbers of bacterial CFUs in the blood (B) and peritoneal lavage fluid (C; n = 9-11/group), numbers of blood and peritoneal neutrophils (D; n = 6-7/group), and levels of TNF-?, IL-6, MCP-1, and IL-12 in the plasma 18 h after CLP (n = 9-11/group). Results in B-D show values from individual mice; bars indicate means ± SEM, Responses of MPO-deficient mice in models of polymicrobial sepsis and LPS-induced endotoxemia, systemic quantification of MPO-induced bioluminescence, and levels of neutrophils after adoptive transfer in PMN WT versus PMN DTR mice
, Quantification of CD62L and CD11b levels (geometric mean fluorescence intensity [GeoMean]) on Ly6G + CD11b + blood neutrophils before (time 0) or 6 h after injection of LPS in WT or Mpo ?/? mice. (G) Percentage of blood neutrophils before (time 0) and 20 h after LPS injection (25 mg/kg) in WT and Mpo ?/? mice. F and G show values from individual mice; bars indicate means ± SEM pooled from two (F) or three (G) independent experiments (total n = 5-15/group). (H) Levels of TNF-?, IL-6, IL-10, IFN-?, and MCP-1 in the plasma of WT and Mpo ?/? mice before (time 0) and 6 h after LPS injection, versus WT group by Mantel-Cox log-rank test (A) or Mann-Whitney U test (B-E). (F)
, (I) Quantification of MPO-induced bioluminescence in the stomach, cecum, duodenum, kidney, and heart 6 h after i.p. injection of PBS (in WT mice) or LPS (25 mg/kg) in WT mice, Mpo ?/? mice, DT-treated PMN DTR mice, and DT-treated PMN WT littermate controls, and 5 min after luminol injection. Data are means + SEM from three independent experiments (total n = 6-14/group) except for Mpo ?/? mice
,
, Cells were >80% YFP + on average for all adoptive transfer experiments (K and L). Various numbers of purified neutrophils were transferred i.v. into DT-treated PMN DTR mice (in which endogenous YFP ? neutrophils were depleted) or DT-treated PMN DTR mice (which contained endogenous YFP ? neutrophils), versus PBS-treated WT group, and # , P < 0.05 versus corresponding LPS-treated control group by unpaired Student's t test. N.S