ACE plays a physiological role in antibacterial defense. (A) Neutrophil ACE expression in response to MRSA stimulation. WT mice were injected IV with MRSA. After 48 hours, ACE expression was determined in CD11b⁺Ly6G⁺ neutrophils by FCM. The figure is representative of 5 mice. ACE expression was increased in both blood and splenic neutrophils following MRSA infection. (B) Resistance to MRSA infection in WT (◊) and ACE KO (Δ) mice. Groups of mice were infected subcutaneously with MRSA (1 × 10⁷ CFU/mouse flank). (i) Skin lesion area per day postinfection, (ii) Bacterial burden in individual lesions on day 3 postinfection. (C) Bacterial resistance following transplantation of either WT or ACE KO BM. (i) Representative image of skin lesions at day 3 post-infection, (ii) Skin lesion area, (iii) Bacterial burden per lesion. (D) In vitro MRSA clearance by blood from WT mice or ACE KO mice. Following infection with ∼10⁶ CFU/mL MRSA, blood samples from mice were assessed for their ability to eliminate MRSA after 2 or 5 hours of incubation. (E) In vitro intracellular killing of MRSA in neutrophils purified from bone marrow. Intracellular killing was significantly lower in ACE KO compared with WT neutrophils (n = 8/group). *P ≤ .05, **P ≤ .005, ***P ≤ .0005.