Figure 1. Deletion of TRPM2 Enhances Neutrophil-Mediated Vascular Injury.

(A) LPS-induced microvascular injury in the classical local Shwartzman reaction (LSR) induced by consecutive injections of LPS followed by TNF-α. n = 3–4 mice per condition. Scale bar, 5 mm.

(B) The extent of hemorrhage was determined in WT and Trpm2^−/− mice through densitometric analysis of skin samples receiving either LPS or PBS injections. Mean ± SEM. *p < 0.05.

(C) H&E-stained skin sections from WT (upper panels) and Trpm2^−/− (lower panels) mice treated with LPS or PBS, as indicated, are shown. Erythrocyte extravasation, thrombus formation, and neutrophil accumulation are evident in the images from LPS-treated Trpm2^−/− mice. Scale bar, 100 μm.

(D) Tissue MPO activity in the skin of mice from the WT and Trpm2^−/− groups. Mean ± SEM. **p < 0.01.

(E) Tissue MPO activity in the lungs of WT and Trpm2^−/− mice 4 hr after fMLF stimulation. Mean ± SEM. *p < 0.05 (Student’s t test). n = 3–4 mice per condition.

(F) Naphthol AS-D chloroacetate staining of lung sections from WT and Trpm2^−/− mice obtained after fMLF challenge. No neutrophils were observed in untreated mice (left panels). fMLF-treated Trpm2^−/− mice (right panels) showed greater neutrophil infiltration in the lungs. Arrowheads indicate infiltrating neutrophils. Scale bar, 50 μm.

Data are representative of (A), (C), and (F) or are from (B), (D), and (E) three independent experiments.