Figure 2.
ASA treatment reduces infection-induced coagulopathy but did not affect pathogen clearance. (A) Quantitative analysis of thrombin probe fluorescence within the liver microcirculation of control mice, S aureus–treated mice, or S aureus–treated mice that received ASA 1 hour prior infection (N = 3-4). Values represent the percentage of an FOV occupied by the fluorescent probe. (B) TAT complex plasma levels in control mice, S aureus–infected mice, and mice treated with ASA 1 hour prior to, or 3 hours after, infection (N = 7-9). (C) Mice were injected with fluorescein isothiocyanate–dextran as a contrast agent to identify perfused liver vasculature in S aureus–infected mice (i), in S aureus–infected mice pretreated with ASA (ii), or mice treated with ASA 3 hours after infection (iii). (iv) Quantification of the percentage of an FOV occupied by occluded vessels (N = 4-5). Liver vasculature was stained by IV injection of fluorescently-conjugated dextran (green); scale bar, 50 μm. (D-H) ALT (D) and AST (E) were quantified in plasma of control and S aureus–infected mice with and without ASA treatment (N = 3-10). After 6 hours of infection, the liver (F), lungs (G), and spleen (H) were collected and bacterial CFUs were measured in infected and ASA-treated mice (N = 5-10). Values are presented as the number of CFUs per gram of tissue. (I) Representative images of sterile bead capture from the circulation by KCs in control (i) and ASA-treated mice (ii) (N = 3). Quantification of bead capture by KCs in control and ASA-treated mice (iii). (J) Representative images of ROS production by KCs in control infected (i) and ASA-pretreated mice infected with S aureus (ii). Quantification of ROS+ KCs in infected control and ASA-treated mice (iii) (N = 3-6). (I-J) Labelling of cells in vivo was achieved by IV injection of fluorescently-conjugated antibodies against F4/80 (Kupffer cells; blue). Flurescent polystyrene beads were injected IV (green) in panel I whereas dihydroethidium was injected IV in panel J. Dihydroethidium is converted to a precipitant in the presence of ROS (red); scale bar, 50 μm. Values represent the percentage of KCs per FOV that stain positive for ROS production. Values represent the mean obtained from at least 5 FOVs in each animal. Data are represented as mean plus or minus SEM. Statistical analysis was conduced using a 1-way ANOVA with a post hoc Tukey test for panels A-B, Civ, D-H, and Jiii and a Student t test for Iiii. ***P < .001 vs control; #P < .05, ##P < .01, ###P < .001 vs S aureus.

ASA treatment reduces infection-induced coagulopathy but did not affect pathogen clearance. (A) Quantitative analysis of thrombin probe fluorescence within the liver microcirculation of control mice, S aureus–treated mice, or S aureus–treated mice that received ASA 1 hour prior infection (N = 3-4). Values represent the percentage of an FOV occupied by the fluorescent probe. (B) TAT complex plasma levels in control mice, S aureus–infected mice, and mice treated with ASA 1 hour prior to, or 3 hours after, infection (N = 7-9). (C) Mice were injected with fluorescein isothiocyanate–dextran as a contrast agent to identify perfused liver vasculature in S aureus–infected mice (i), in S aureus–infected mice pretreated with ASA (ii), or mice treated with ASA 3 hours after infection (iii). (iv) Quantification of the percentage of an FOV occupied by occluded vessels (N = 4-5). Liver vasculature was stained by IV injection of fluorescently-conjugated dextran (green); scale bar, 50 μm. (D-H) ALT (D) and AST (E) were quantified in plasma of control and S aureus–infected mice with and without ASA treatment (N = 3-10). After 6 hours of infection, the liver (F), lungs (G), and spleen (H) were collected and bacterial CFUs were measured in infected and ASA-treated mice (N = 5-10). Values are presented as the number of CFUs per gram of tissue. (I) Representative images of sterile bead capture from the circulation by KCs in control (i) and ASA-treated mice (ii) (N = 3). Quantification of bead capture by KCs in control and ASA-treated mice (iii). (J) Representative images of ROS production by KCs in control infected (i) and ASA-pretreated mice infected with S aureus (ii). Quantification of ROS+ KCs in infected control and ASA-treated mice (iii) (N = 3-6). (I-J) Labelling of cells in vivo was achieved by IV injection of fluorescently-conjugated antibodies against F4/80 (Kupffer cells; blue). Flurescent polystyrene beads were injected IV (green) in panel I whereas dihydroethidium was injected IV in panel J. Dihydroethidium is converted to a precipitant in the presence of ROS (red); scale bar, 50 μm. Values represent the percentage of KCs per FOV that stain positive for ROS production. Values represent the mean obtained from at least 5 FOVs in each animal. Data are represented as mean plus or minus SEM. Statistical analysis was conduced using a 1-way ANOVA with a post hoc Tukey test for panels A-B, Civ, D-H, and Jiii and a Student t test for Iiii. ***P < .001 vs control; #P < .05, ##P < .01, ###P < .001 vs S aureus.

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