Figure 4. MMP28 contributes to pulmonary fibrosis and M2 polarization in the lung.

(A) Mice received bleomycin and were followed for weight change as a marker of severity of illness (n=8–10 mice/genotype/condition). Mmp28−/− mice had earlier recovery of weights between Days 7 and 9. (B) In a separate experiment using high-dose bleomycin (n=11/genotype), WT mice trended toward greater mortality (P=0.12), and (C and D) surviving WT mice had greater area of lung involvement compared with Mmp28−/− mice, as determined using H&E-stained lung tissue and Visiopharm software. (E and F) Lung collagen was localized and quantified using Picrosirius Red Sircol assay on lung tissue and homogenates. (E) Lung histology at Day 14 demonstrates collagen deposition (red fibers) in WT and Mmp28−/− lungs but with greater involvement in WT lungs. (F) Homogenized lungs analyzed for collagen content demonstrate collagen accumulation in both genotypes at Days 14 and 21 but with a blunted response in Mmp28−/− mice. (G–I) Quantification of BAL total, macrophage, and neutrophil cell counts at Days 3, 7, and 14. Early after bleomycin (Day 3), WT and Mmp28−/− mice had a similar inflammatory response. At Day 7, the Mmp28−/− mice had increased macrophage recruitment and fewer neutrophils. At Day 14, greater macrophage influx in Mmp28−/− mice persisted. *P < 0.05.