Oxygen-Independent Antimicrobial Systems in Polymorphonuclear Leukocytes

Abstract

It has long been recognized that neutrophil polymorphonuclear granulocytes (PMN) exercise antimicrobial action only at very short range, and that they must attach to and ingest their targets in order to kill them with maximum efficiency. Metchnikoff (1905) first recognized this. Kanthack and Hardy (1894) extended Metchnikoff’s ideas to show the importance of degranulation of cytoplasmic granules. They showed that bacilli stopped growing only when they came in contact with and degranulated guinea pig granulocytes. Bacilli in the same fluid untouched by granulocytes continued to grow logarithmically. Remarkably, Kanthack’s work was forgotten. But Hirsch (1962) and Zucker-Franklin (Zucker-Franklin and Hirsch, 1964) rediscovered and extended these concepts, emphasizing the importance of the phagolysosomes formed about microbes as they are endocytized by heterophil (or neutrophil) polymorphonuclear granulocytes. Their studies focused attention on the importance of substances carried by cytoplasmic granules and deposited in phagolysosomes of PMN. It is now generally agreed that there are two principal granule classes, the specific granules and the azurophil granules (Bainton and Farquhar, 1968; Ullyot et al, 1973). The granules are now known to comprise several antibacterial substances including cationic antibacterial protein (CAP), lysozyme (LYZ), lactoferrin (LF), and myeloperoxidase (MPO). The distribution of several of these substances in the granules is shown in Table 1.