Fig. 5. C5aR1-deficient mice display dysregulated hepatocyte caspase-3 activation and impaired compensatory proliferation in the regeneration phase of APAP-induced ALI.

a–d C57BL/6J C5aR1-deficient mice and their wild-type counterparts received 0.9% NaCl (control groups) or APAP (300 mg/kg). After 30 h, liver tissue was evaluated for the presence of active cleaved caspase-3 by immunohistochemistry. Representative results are shown for vehicle-treated wild-type (a, n = 7), vehicle-treated C5aR1-deficient (b, n = 7), APAP-treated wild-type (c, n = 10), and APAP-treated C5aR1-deficient mice (d, n = 12). e Quantification of cleaved caspase-3-positive nuclei detectable in APAP-treated wild-type (n = 10) and C5aR1-deficient mice (n = 12). Positive nuclei (almost exclusively found within/adjacent to necrotic regions; exemplarily indicated by yellow arrows) were counted and related to the percentage of necrotic area in the respective liver segment (^#p < 0.05). Statistical analysis on raw data: e Student’s t-test, data are shown as means ± s.e.m. f–h C5aR1-deficient mice and their wild-type counterparts received APAP at 300 mg/kg. After 30 h, mice were sacrificed and liver tissue was analyzed. f, g Nuclear PCNA protein was determined by immunohistochemistry. Representative results are shown for APAP-treated wild-type mice (f, n = 9) and C5aR1-deficient mice (g, n = 11). h PCNA-positive nuclei (exemplarily indicated by yellow arrows) were counted per field of vision and are shown as means ± s.e.m. (^##p < 0.01). Statistical analysis on raw data: Student’s t-test. Wild-type mice, WT; knockout mice, KO. Scale bars: 50 μm.