Figure 5.

GRP blockade diminishes or abrogates many cellular mechanisms after radiation. At 4 weeks after radiation, the data indicate that GRP increases CD68⁺ macrophages because GRP blockade with 77427 abrogates the increase and macrophages are GRPR⁺. At 6 weeks after radiation, GRP promotes increased numbers of GRP⁺/PGP9.5⁺ pulmonary neuroendocrine cells (PNECs) consistent with multipotent (plastic) epithelial cells [airway (AR) epithelium is GRPR⁺]. At 10 weeks after radiation, there is increased expression of pSmad2/3, indicating activation of TGF-β signaling. At 20 weeks after radiation, early interstitial fibrosis is evident as SMA⁺ myofibroblasts and collagen deposition in alveolar septa (pulmonary fibroblasts are GRPR⁺). All these functional and/or phenotypic changes are reversed by GRP blockade.