Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis
J. Clin. Invest. Ashok N. Babu, et al. 117:3774 doi:10.1172/JCI32311 [Go to this article.]

Figure 7
Injured and nonperfused endothelium is a marker for injury severity that cannot be rescued by immunosuppression. (A) Tissue oximetry was performed using a microprobe to detect tracheal epithelial pO₂. Syngrafts maintain consistent tissue oxygen content, whereas allografts develop relative tissue hypoxia by 10 day. (B) Allografts (BALB/c→B6) were allowed to undergo varying durations of rejection, at which point they were retransplanted to naive immunosuppressed B6 animals for an additional 28 days. H&E-stained axial sections were used to measure the ratio of subepithelial height to epithelial height. This measure has been validated previously as correlating strongly with chronic rejection histologic scoring (9). Syngeneic grafts that were retransplanted maintained a normal ratio of approximately 1. Rejection durations of 10 day or longer resulted in severe airway remodeling despite rescue therapy (n = 5/group). *P < 0.05 versus all other groups. (C) Axial section of allograft following 6 days rejection. (D) EM demonstrating normal appearance of vascular endothelium in an allograft following 6 days rejection. (E) Axial section of allograft that underwent 6 days of rejection prior to retransplantation to a naive immunosuppressed animal demonstrating rescue with normal histology. (F) Axial section of allograft following 10 days rejection. (G) EM demonstrating abnormal appearance of vascular endothelium with red blood cell extravasation in an allograft following 10 days rejection. (H) Axial section of allograft that underwent 10 days of rejection prior to retransplantation to a naive immunosuppressed animal demonstrating lack of rescue due to flattened epithelium and subepithelial fibrosis. Original magnification, ×20 (C, E, F, and H); ×1,100 (G).