How do Cavity Macrophages Migrate?

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Very primitive organisms have a cavity or sack filled with fluid. Animals also have cavities where the vital organs reside. The common link is that in all these cavities live specialized cells known as coelomocytes in simple organisms such as sea urchins and macrophages in more developed animals such as mice. Ironically, we know a lot about the coelomocytes that migrate to perturbations in the cavity and repair tissue or eat invading bacteria while in mammals very little is known about the biology of macrophages in the cavities. Instead, because of the relative ease of macrophage isolation from the peritoneal cavity (which harbors the liver, spleen, intestines, etc), thousands of studies have been published about all the pathways and proteins these cells express in test tubes. Last year we published one of the first functional studies on these cells in vivo and showed that when a critical organ is perturbed, these cells migrate to the site and help to heal. However, almost nothing is known about what these cells do under normal conditions and how they detect that a perturbation is occurring. Finally, during a peritoneal infection in the cavity, these macrophages disappear and new small macrophages come in from bone marrow and help to eradicate the infection. To date, it has been impossible to visualize these cells without opening up the cavity and at that point everything is perturbed. As such we have purchased a special microscope where near infrared lasers penetrate deep into the cavity so we can see these cells without having to do any surgery.***We hypothesize that peritoneal macrophages patrol the peritoneal cavity like policemen constantly checking all of the organs for perturbations under normal conditions. Whether they swim or crawl or float freely across organs will be assessed using our new two photon microscope. If they are crawling on tissues they need “hands” (adhesive proteins). We will figure out what these adhesive proteins are. If the organ is perturbed the macrophages quickly detect the perturbation and move to the afflicted site. We know lots about how immune cells crawl in tissue, the same principles may not apply in the fluid of cavities. Using our powerful microscope we will explore the signaling molecules and adhesion molecules that allow them to move to sites of perturbation. Finally, we will also explore what happens to these peritoneal macrophages during bacterial invasion, known as the macrophage disappearance reaction. We will use imaging to determine whether they truly leave the cavity and disappear or just instantaneously stick firmly to the surfaces of the cavity and therefore are no longer found in the fluid. These studies will advance our understanding of the biology of these enigmatic cells found in all species of invertebrates and vertebrates. We will provide important information about how these cavity macrophages behave and function under normal conditions and when organs are perturbed.