Mouse model of foreign body reaction that alters the submesothelium and transperitoneal transport

Abstract

To address the hypothesis that sterile intraperitoneal (ip) catheters alone promote a progressive foreign body reaction (FBR), silicone catheters were surgically implanted in C57BL mice. Controls (CON) underwent sham operations. After 1–5 wk (E1–E5 for catheter-bearing mice), catheters were recovered, and the adherent cell layer (ACL) was separated and cultured to demonstrate sterility. Transperitoneal transport experiments were performed to determine the mass transfer coefficients of mannitol (MTCM) and albumin (MTCA) and the osmotic filtration flux ( Josm). After euthanasia, tissue samples were analyzed for submesothelial thickness, angiogenesis, and cytokine immunohistochemistry (IHC). Progressive increases with time were observed in submesothelial thickness (μm: CON, 18.8 ± 12.3; E1, 46.1 ± 20.0; E2, 72.0 ± 17.9; E4, 97.3 ± 20.0; E5, 131.7 ± 10.3; P < 0.003), angiogenesis (no. of vessels/mm of peritoneum: CON, 10.7 ± 9.4; E1, 15.4 ± 15.6; E2, 27.0 ± 14.0; E4, 39.8 ± 15.7; E5, 90.1 ± 8.1; P < 0.0003), MTCA(6.5 ± 1.5 × 10−5cm/min, mean CON; 18.0 ± 1.1 × 10−5cm/min, mean E1–E5, P < 0.0001), Josm(0.0013 ± 0.0001 cm/min, mean CON; 0.0017 ± 0.0001 cm/min, mean E1–E5, P < 0.01). No significant differences were found for MTCM. IHC demonstrated strong staining for all treated animals and correlated with the ACL. This mouse model demonstrates that ip silicone catheters result in progressive FBR, altering the submesothelial anatomy and transperitoneal transport, and will form the basis for mechanistic studies in genetically-altered animals.