Historical background

The ability of certain leukocytes to ingest and kill microorganisms was established over a century ago by Eli Metchnikoff, a comparative zoologist who coined the terms 'phagocytosis' and 'phagocyte'. Metchnikoff had recognized the central importance of phagocytosis in host defense and vigorously proselytized the community of fin-de-siƩcle protoimmun-ologists on its behalf. In 1891, Hankin reported 'it is possible to obtain from cells that are or can become phagocytes a substance having bacteria-killing powers'. Many investigators attempted to define this substance in the ensuing years. Although the rudimentary technology available for protein purification generally restricted the success of early efforts, it did not preclude the creation of memorable names, such as 'leukins' and 'phagocytin', to describe these uncharacterized molecules. With the exception of the noteworthy discovery of lysozyme by Sir Alexander Fleming in 1922, the modern delineation of oxygen-independent microbicidal mechanisms began in the 1960s when Zeya and Spitznagel reported that rabbit and guinea pig neutrophils contained a group of relatively small 'lysosomal cationic proteins' that exhibited a broad spectrum of antimicrobial activity in vitro. Although the significance of this discovery was overshadowed by the concomitant delineation of oxidative microbicidal mechanisms in phagocytes and by the delay in finding the human counterparts of these peptides ('defensins'), interest in the endogenous antimicrobial molecules of phagocytes has increased sharply during the past few years. Because much of the available information about nonoxidative ('oxygen-independent') mechanisms was derived from work on human neutrophils, these cells will be a principal focus of this section. More recently, antimicrobial peptides and proteins have been demonstrated in epithelial cells and secretory glands of the genitourinary, respiratory and digestive tracts, suggesting that such molecules play important roles in defending moist, mucosal surfaces throughout the body.

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