Figure 7: The effects of COX1 knockout and aspirin on platelet-dependent inhibition of inflammation and protection against sepsis.
(a,b) C57BL/6 mice received i.p. injection of LPS (10 mg kg−1), immediately followed by retro-orbital injection of saline or 1 × 109 platelets from COX1-deficient mice (COX1−/−) or wild-type littermates (COX1+/+) in 0.2 ml saline. Blood was collected before or at 1, 2, 4 and 8 h after LPS injection. TNF-α (a) and IL-6 (b) concentrations in plasma were measured. Values are means±s.d. (n=5). Differences between two groups were assessed using unpaired two-tailed Student’s t-test. (c) C57BL/6 mice received i.p. injection of LPS (10 mg kg−1), immediately followed by retro-orbital injection of 1 × 109 platelets from either COX1 knockout mice or wild-type littermates in 0.2 ml saline or saline. Survival rate was observed for 3 days. P<0.001 between control group and the group injected with wild-type platelets; P>0.2 between control group and the group injected with COX1−/− platelets by Wald’s test. (d) C57BL/6 mice received i.p. injection of aspirin (10 or 25 mg kg−1). Blood was collected at 30 min after aspirin injection. Washed platelets were incubated with thrombin (0.1 U ml−1) for 5 min, and TXB2 in the supernatant was measured by enzyme-linked immunosorbent assay kit and expressed as relative to platelets from control mice (without aspirin injection) in the absence of thrombin. Values are means±s.d. (n=3). Differences between two groups were assessed using unpaired two-tailed Student’s t-test. (e,f) C57BL/6 mice received i.p. injection of aspirin (25 mg kg−1) 30 min before i.p. injection of LPS (10 mg kg−1). Blood was collected before or at 1, 2, 4 and 8 h after LPS injection. TNF-α (e) and IL-6 (f) concentrations in plasma were measured. Values are means±s.d. (n=6). Differences between two groups were assessed using unpaired two-tailed Student’s t-test. (g) C57BL/6 mice received i.p. injection of aspirin (25 mg kg−1) at 30 min before i.p. injection of LPS (10 mg kg−1). Survival rate was observed for 3 days. P-value was calculated by Wald’s test in a discrete time hazard model using version 9.2 of SAS software.
