Antibiotic proteins of human neutrophils.

Despite strenuous opposition, Ilya Metchnikov convinced the scientific world 1 10 years ago that phagocytosis has a major role in immunity to infection (1).' Metchnikov conjectured that phagocytes destroy microbes with their enzymes, or cy- tases as he called them, but proof of this had to wait for new tools. The field moved when Cohn and Hirsch (1) revealed the role of degranulation in phagocytosis. Hirsch described pha- gocytin (1). Spitznagel and Chi (1) and Zeya and Spitznagel (1) showed that phagocytin is not one but an array ofantibacterial proteins, uniquely cationic, associated with cytoplasmic gran- ules, and coated on bacteria during phagocytosis. Klebanoff described the myeloperoxidase (MPO),2 H202, Cl-antimicro- bial system (1), and Gray described the oxidative defect in neutrophils and monocytes of children with X-linked chronic granulomatous disease (2). The duality of the killing mecha- nisms, oxygen independent and oxygen dependent, and the association of many of their components with cytoplasmic granules became accepted. I deal here with one aspect of research on oxygen-independent mechanisms, the antibiotic proteins of human neutrophils. These proteins comprise at least three structurally different families that share the capacity to kill bacteria independent of oxygen and evidently, contrary to Metchnikov's conjecture, to do so independent of enzymic action.