The potential role of innate immunity in the pathogenesis of post-operative adhesions

THE POTENIAL ROLE OF INNATE IMMUNITY IN THE PATHOGENESIS OF POST-OPERATIVE ADHESIONSbyJENNELL WHITEDecember 2011Advisor: Ghassan SaedMajor: PhysiologyDegree: Doctor of PhilosophyPost-operative adhesion development occurs in the vast majority of patients followingabdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bandsmay form within the first 5-7 days post-surgery and have the ability to cause a distortion in thenormal anatomical positioning of abdominal organs. Consequently, adhesions are majorcontributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain.Physiological processes responsible for adhesion formation remain obscure though it is believedto involve cell migration, proliferation, and differentiation of several cell types includingmesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released fromthese cells regulate fibrinolytic activity, tissue remodeling, angiogenesis, and extracellular matrixturnover, processes that are known to be central to the development of adhesions. Our long-termgoal is to prevent or selectively limit the development of post-operative adhesions. The objectiveof this study is to determine the role that macrophages play in the development of post-operativeadhesions. Our central hypothesis states that surgical-induced hypoxia triggers a pro-inflammatory signal, leading to the activation and recruitment of resident and infiltratingmacrophages, which contribute to the development of the adhesion phenotype. This hypothesis