Figure 2. Inhibition of BLT1, but not BLT2, improves host defense in diabetic mice during MRSA skin infection.

(A) WT CT, STZ-treated WT, STZ-treated Alox5^–/–, and STZ-treated Ltb4r1^–/– mice were infected s.c. with MRSA, and infection areas were measured for 9 days. (B) Bacterial CFUs in the skin at day 9 after infection. Data are mean ± SEM of 5–10 mice. *P < 0.05 vs. WT CT mice. ^#P < 0.05 vs. STZ-treated WT mice. (C) CT and STZ-treated mice were infected s.c. with MRSA. STZ-treated mice were treated daily with topical ointments, vehicle-control, 0.001% BLT1 antagonist (U-75302), or 0.001% BLT2 antagonist (LY255283), and infection area was measured as in A. (D) Bacterial CFUs from mice in C at day 9 after infection. Data are mean ± SEM of 4–6 mice. *P < 0.05 vs. CT mice. ^#P < 0.05 vs. STZ-treated mice treated with vehicle control ointment. (E) Mice were infected s.c. with bioluminescent-expressing MRSA. Infection areas were measured every other day in CT and STZ-treated mice treated daily with vehicle control or 0.001% BLT1 antagonist (U-75302) ointments. (F) Bioluminescence imaging (BLI) to quantify bacterial burden in the skin at days 1, 3, 4, 7, and 9 after infection. (G) Representative images of bioluminescent MRSA infection in control and diabetic mice that were treated or not with BLT1 antagonist scanned by BLI. (H) Lesion size of nondiabetic NOD (ctNOD) and diabetic NOD (dbNOD) mice infected with MRSA by s.c. injection. Infected dbNOD mice were treated daily with vehicle-control or 0.001% BLT1 antagonist (U-75302) ointments as in C. Data are mean ± SEM of 5–10 mice. *P < 0.05 vs. CT mice. ^#P < 0.05 vs. STZ-treated mice treated with vehicle control. (I) Gram stains of CT and diabetic mice that were infected and treated with the BLT1 antagonist with MRSA for 1 and 9 after infection. Top panels show 100× and bottom panels show 1,000× magnification with an inset of a cropped zoomed view of 5 ,000× magnification. Arrows indicate bacteria.