Figure 6. Thrombin inhibitor reduces macrophage fusion but does not affect capsule formation.

(A) Representative confocal images showing that treatment with argatroban, as compared with the untreated control, reduces FBGC formation. Argatroban (9 mg/kg and 18 mg/kg; termed argatroban 1 and 2, respectively) was injected i.p. in WT mice for 5 days before implantation of materials and continued for 7 days post-surgery. Control mice were injected with PBS. (B) Granulation tissue formed around implants was stained with H&E. (C) Macrophage fusion was assessed as a fusion index. Five to six random 20× fields were used per sample to count nuclei. (D) The number of nuclei in FBGCs on the surface of implants retrieved from control and argatroban-treated mice. Approximately 70-140 FBGCs on each implant were counted. (E) The frequency distribution of nuclei in FBGCs on implants retrieved from control mice and mice treated with 18 mg/kg argatroban. (F) Spreading of FBGCs on the surface of explants retrieved from control mice and mice treated with 18mg/kg argatroban. Six to eight random 20x fields per sample were used to determine the cell surface area (10-15 cells/field). (G) The frequency distribution of the FBGC areas on implants retrieved from control mice and argatroban-treated mice. (H) The thickness of granulation tissue formed on the surface of implants retrieved from control and argatroban-treated mice was determined using ImageJ software. Ten random fields were used per sample to measure the thickness of cross-sections. Results shown are mean ± S.D. from three independent experiments. n=6 mice per group. Two-tailed t-test and Mann-Whitney U test were used to calculate significance. ns, not significant, **p < .01, ***p < .001