The interactions between apoptotic cells and macrophages within the murine omentum and peritoneal cavity

• Main Author: Watson, Simon James William
• Published: University of Edinburgh 2008
• Subjects: 616.079
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663543

I began this thesis by examining the rate at which Mφ phagocytosed apoptotic cells <i>in vivo</i> using the murine peritoneal cavity as a model system. I noted that the number of Mφ was not merely a non-specific effect of manipulating the peritoneal cavity but was a consequence of the phagocytosis of apoptotic cells. The mechanism underlying this ‘Macrophage Disappearance Reaction’ (MDR) was investigated and two manipulations – the instillation of hyularonidase enzyme or unfractionated heparin – respectively increased or decreased the magnitude of the MDR without affecting the rate of apoptotic cell clearance. I then turned my attention to the fate of the disappearing Mφ, focusing on the omentum, an organ within the peritoneal membrane highly adapted for the initiation of acute inflammatory reactions and innate immunity. A series of adoptive transfer experiments showed that, after phagocytosing apoptotic cells, intraperitoneal Mφ migrated to specialized coelomic-associated lymphoid tissue (CALT) called ‘Milky Spots’ within the omentum. Further experiments showed that some Mφ subsequently left the peritoneal cavity and migrated to parathymic lymph nodes a known destination for inflammatory peritoneal Mφ during the resolution of peritonitis. I then returned to the starting point of this thesis, ie the rate of phagocytosis of apoptotic cells <i>in vivo</i>, and developed a powerful new <i>in vivo</i> phagocytosis assay using omental milky spots as the experimental model. The hitherto unrecognized role of the omentum in the clearance of peritoneal apoptotic cells and Mφ emigration should increase the level of general scientific interest in the omentum which I believe to be a true organ of innate immunity.