Macrophage Biochemistry, Activation and Function

Functionally and morphologically heterogeneous macrophages are widely scattered in body tissues. They are represented by the alveolar macrophages of the lung, Kupffer cells of the liver, cells found free in the pleural and peritoneal cavities and cells lining the sinusoids of the spleen and bone marrow. This varied group of phagocytic cells, along with monocytes, compose the mononuclear phagocyte system. The phagocytes have their origin in the granulocytic series of the bone marrow where the promonocyte is the earliest recognizable form. This stem cell actively divides and with maturation gives rise to the monocyte. After a short-lived residence in the bone marrow, monocytes are released into the blood where they normally account for 3-5 of the circulating leukocytes. They then leave the circulation, enter the tissues and mature into tissue macrophages. In the process, they increase in size and their mitochondria and components of the vacuolar apparatus become more abundant. Functional capabilities, including phagocytic activity, protein synthesis and surface receptors, also increase. The fully mature macrophase is capable of participating in varied biological and immunological activities, including protecting the tissues against infection by invading microorganisms. In infections, the severity of illness and the ultimate survival of the host depend greatly on how effectively macrophages can perform their microbicidal function. To wage an effective battle against potential pathogens, macrophages undergo a further transformation of their biochemical and physiological properties designed to enhance their microbicidal capacity. The mechanism underlying the enhancement of macrophage functions during infection serves as the them of this chapter.