Figure 3

Effect of caspase inhibition of transforming growth factor (TGF)-β1-induced apoptosis and CD45⁺ collagen (Col)-Iα1⁺ cell accumulation. (a) Cleaved caspase-3 immunohistochemistry (red) in TGF-β1 Tg⁺ mice exposed to vehicle (left) or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD/fmk) (right). Nuclei are counterstained with hematoxylin, 40 × original magnification. A significant reduction in cleaved (activated) caspase-3 is noted in the Z-VAD/fmk treated mice. (b,c) Z-VAD/fmk reduces terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining (b) and CD45⁺Col-Iα1⁺ cells (c) in TGF-β1 Tg⁺ mice. (d-f) Compared to untreated mice, the lungs of TGF-β1 Tg⁺ treated with Z-VAD/ fmk demonstrate unchanged quantities of CD45⁺Col-Iα1⁺CD14^-CD34⁺ cells (d), increased quantities of CD45⁺Col-Iα1⁺CD14⁺CD34⁺cells (e), reduced quantities of CD45⁺Col-Iα1⁺CD14⁺CD34^- cells, and unchanged quantities of CD45⁺Col-Iα1⁺CD14^-CD34^- cells. (h) Accumulation of CD206/MRC⁺ cells is not affected by Z-VAD/fmk. (i) TGF-β1-induced expression of the scavenger receptors MRC (left axis) and MSR-1 (right axis) is not affected by administration of Z-VAD/fmk. N = 5 mice/group. *P < 0.05, **P < 0.01, ***P < 0.001.