Macrophage Puzzles: Macrophages are one of the smallest differentiated cell types in the human body, perhaps the smallest, although "macro" comes from the Greek word for big. When macrophages are circulating in the blood, they are called "monocytes"; when macrophages are embedded in brain tissue, they are called "microglia"; when macrophages are in the liver, they are called "Kupfer cells" (named after a German biologist) and are supposed to digest over-aged red blood cells. Another place where there are many macrophages is inside the alveoli of the lungs, and these are called "dust cells", because they are believed to phagocytize bits of dust that get into the lungs. When T-lymphocytes attack some tissue, macrophages are somehow attracted to the area (probably by chemotaxis), and themselves produce further damage to the tissue being attacked. For example, in people having an multiple sclerosis attack, there are large numbers of macrophages attacking some of their myelin, and phagocytizing pieces of it. Why don't the microglial cells also do this? Osteoclasts are larger, multinuclear cells that are believed to form by fusion of macrophages with each other. The function of osteoclasts is to dissolve bone (solubilizing the calcium phosphate, definitely; and maybe also digesting the collagen?), and your bones are constantly being dissolved in some places and being re-made (somehow) by a different kind of cell, called osteocytes or osteoblasts. When this breakdown process destroys more bone than is being replaced, the result is called osteoporosis, and is a major cause of breakage of bones in older people, especially older women. One treatment for osteoporosis is a drug that works by inhibiting osteoclasts. Is such an inhibition possible for MS? One of the most serious ideas about what goes wrong in atherosclerosis is that macrophages (Maybe of a special kind? Maybe cells that had previously been monocytes?) absorb lots of cholesterol, thereby becoming "foam cells", stick to the inner lining of arteries, and then crawl from there in among the smooth muscle cells of the "tunica media", and then either stay there or die and release the cholesterol. An alternative possibility might be that macrophages crawl in among the smooth muscle cells, and then accumulate the cholesterol? Because we know what osteoclasts do to bone, we should give more thought to whether foam cells are also digesting the collagen fibers that provide much of the strength of artery walls. Given that atherosclerotic "plaque" has the physical "feel" of brittle cheese, something must be digesting that collagen, and the foam cells may be doing something worse than just taking up space. Can this digestion be inhibited? Recently, I have read a possibly-true medical claim that all (or most?) of the tissues of our body are infiltrated with various sub-types of macrophages, and that these are about 10% of either the number of cells or the total volume of cells (I think the former is more likely) of every tissue. This idea of each and every tissue having its own equivalent of microglia was new to me, although I had known about brain and liver, but will cause me to look at tissue sections more carefully. When programmed cell death occurs, it is said that macrophages quickly gobble up the debris of the dead cells; and that can't very well happen unless there are macrophages there. Continuing this line of thought, one wonders if smooth muscle cells are among those that have 10% content of macrophages, and then ask if that 10% macrophage content business also applies to the tunica media of arteries. In other words, were those foam cells already there, embedded in the tunica media before they developed all those vacuoles and looking like foam? How could you discover the answer? Experiments and testable hypotheses about macrophages. A possible reason why macrophages don't round up and detach in response to trypsin or other proteolytic enzymes! Their normal function includes digesting and phagocytizing proteins. Therefore it would be a problem for them to be caused to detach and withdraw by the enzymes that they use to digest collagen and other proteins. They need to be insensitive to such enzymes in order to serve their function of digesting and ingesting proteins. It is another question by what method macrophages avoid the usual sensitivity that all other cell types have to proteolytic enzymes. Three categories of possible explanation would be 1) That macrophages use some fundamentally different adhesion method (like maybe they really do stick by van der Waals' forces?); 2) That macrophages lack those integral membrane protein receptors, partial digestion of which somehow induces weakening of cortical cytoplasm in all other cell types; 3) That macrophage cytoplasm doesn't weaken, even when membrane receptors are partially weakened. RGD Peptide: Will it cause detachment of macrophages from glass, plastic and collagen? Or will this be another example in which macrophages behave the opposite of all other cell types. Would macrophage traction become stronger or weaker in response to colchicine, vinblastine and other microtubule poisons. This could be yet another example in which the behavior of macrophages is the opposite from that of all other differentiated cell types. Use roughened plastic as a way to separate macrophages from other cell types dissociated from bones, arteries, brain (microglia), or any other tissue. In particular, will isolated "foam cells" accumulate along roughened lines on polystyrene surfaces, in the way that monocytes and Kupfer cells do?