Macrophage Population Dynamics
Background
Osteoporosis, Alzheimer’s Disease and atherosclerosis are superficially very different disease processes. But although they affect very different tissues and organ systems, they have a surprising number of features in common: all three are prevalent diseases affecting many, if not most, people at least in longer lived societies. All three are also slowly progressive degenerative diseases of the elderly in which the healthy tissue architecture set up during development is gradually lost. At a cellular and molecular level, too, there are as many similarities as differences: epidemiologically, the risk of all three diseases is higher among individuals with higher plasma LDL-cholesterol levels, and all three seem to be associated with the genotype at a single gene locus, the apoE gene. Finally, all three have an inflammatory component, and the role of macrophage trafficking plays an important, if occasionally neglected, role in the disease pathogenesis.
Macrophages play a key role in almost every healthy tissue in the body. They patrol mucosal surfaces (such as skin and gut) where they often act as early warnings of infection. On encountering foreign antigen, they contribute to the early signals that recruits other leukocytes to the site and initiates an acute inflammatory reaction. Once activated, they are also able to mount an effective defence themselves: they are voracious phagocytes capable of ingesting large quantities of foreign material in the tissue.
Some macrophages play a central role in physiological processes independent of the immune system. Their effective phagocytyosis function, so useful for engulfing pathogens, can be turned to other uses. For example, the osteoclast cells in bone which are responsible for degrading the bone matrix to allow turnover essential to maintain structural integrity, are specialised macrophages. Their phagocytotic capacity is directed to bone resorption rather than pathogen elimination. Similarly, macrophages in other tissues are important for clearing out apoptotic cells and thereby maintaining normal tissue architecture. Once again, their phagocytotic capacity has been utilised to a different end.
As a result, the mechanisms which control the number of macrophages present in a wide range of tissues occupies a central nexus in our physiological homeostasis. Failure to maintain the right number of tissue macrophages will ultimately lead to chronic breakdown of tissue architecture. In bone, misregulation of osteoclast number can lead to osteoporosis (low bone mineral density). In brain, misregulation of microglia (the name given to brain tissue macrophages) can contribute to neurodegeneration.