Neutrophil killing of bacteria by oxygen-independent mechanisms: a historical summary.

The historical development of the concept of neutrophil killing of bacteria by oxygen-independent mechanisms is traced. The role of oxygen-independent microbicidal mechanisms in relationship to neutrophil management of microbes is critically evaluated. In the ultrastructural sense, oxygen-independent killing of bacteria requires the deposition of a bactericidal component (granule proteins) or the establishment of a hostile, non-physiologic environment in the phagolysosome. Accordingly, this review is concerned with the identification and cellular location of cationic proteins that participate in nonoxidative killing of gram-negative bacteria by human polymorphonucleur neutrophil granulocytes. Studies reviewed support the hypothesis that oxygen-independent mechanisms function in vivo and are important in host defense against infection. The chemistry of antimicrobial proteins, the biologically active site of each protein, and the mechanism by which the proteins trigger bacterial death all need to be determined at the molecular level.