Chronic Inflammation and Metabolic Stress
Macrophages are associated with various tissues and either derive from monocytes circulating in the blood or from self-renewing embryonal cell populations. They show a large variety of stimulus- and tissue-specific functions, of which the extremes are pro-inflammatory M1-type and anti-inflammatory M2-type macrophages. M1 macrophages are key cells in the initiation of the acute inflammatory response, while M2 macrophages are resolving inflammation and coordinate tissue repair. However, tissue inflammation is not only caused by bacterial infection or tissue injury but may also derive from changes in the concentration of nutrients and metabolites. In this case, the immune system cannot cope the primary stimulus, so that chronic inflammation develops. This metabolic stress, in contrast to infectious or traumatic stress, is often caused by lipid overload in the blood and in adipose tissue. This again is a hallmark of age-related metabolic diseases, such as obesity, insulin resistance and atherosclerosis. For example, hypercholesterolemia (Sect. 11.3) causes stress to macrophages and their associated cells. Moreover, perturbations of the homeostasis of nutrient metabolism dys-regulate functions of the liver.
In this chapter, we will present monocytes and macrophages as the key players in acute and chronic inflammation. We will provide molecular and cellular details of examples of metabolic stress, such as disturbance of reverse cholesterol transport and ER stress. In this context, we will discuss macrophages as important therapeutic targets.