PHAGOCYTES IN HEALTH AND DISEASE

Phagocytic cells are critical for defense against infection, but also play a key role in inflammation. Phagocytic cells engage in obligatory events, including attachment to blood vessel walls, activated chemotaxis, phagocytosis, and microbial killing. Attachment to blood vessels and extracellular membrane proteins depends on the activity of receptor proteins in the integrin class. In addition, phagocytic cells can recognize platelet-activating receptor and PADGEM protein presented by endothelial cells. Chemotaxis has been most widely studied to understand the transduction process. Activated chemotaxis depends on the interaction between GTP-binding proteins (leading to activation of phospholipase C or D), alteration of cellular calcium, and protein kinase-mediated phosphorylation of substrates. Phagocytosis depends on immunoglobulin and complement. It has been recognized that the phagocytosis of some opportunistic pathogens such as mycobacteria and legionella depend primarily on the third component of complement. Microbial killing depends on formation of reactive oxygen intermediates and microbial proteins. In addition, the formation of nitric oxide by phagocytes has recently received attention because of its importance in the killing of some fungi, protozoa, and tumor target cells. Phagocytes may act as hosts for some intracellular pathogens such as chalamydia and listeria. In addition, cytomegalovirus infects neutrophils and human immunodeficiency virus infects monocytic phagocytes. Difficulty in eliminating infection in these host cells will represent a key part of future antiviral therapy of these diseases.