Nonoxidative antimicrobial reactions of leukocytes

Increasingly abundant evidence supports the hypothesis that PMNs and perhaps alveolar macrophages have antimicrobial mechanisms independent of the presences of molecular oxygen for effective action against an array of bacteria and against some fungi. Eosinophils have mechanisms toxic for schistosomula and Trichinella larvae. In all instances the antimicrobial substances isolated have been cationic proteins and, in PMNs, associated with the azurophil cytoplasmic granules of the PMNs. Several of these substances have thus far demonstrated no enzymic function. Two of these substances are serine proteases but in one, chymotrypsin-like protein, the antimicrobial action depends on the cationic properties of the protein and is independent of the proteolytic action of the substance. In most instances, these proteins are cationic due to relatively large proportions of arginine. In two instances, a large proportion of lysine is present. All have high proportions (about 50%) of hydrophobic amino acid. Such proteins occur in the PMNs of man, rabbit, guinea pig, rat, cow, and chicken. The present view is that they are most active against gram-negative bacteria. At least two of them-37-kd and 57-kd proteins (Shafer and Spitznagel, 1983)-act on S. typhimurium in a manner analogous to that of polymyxin B through binding to lipid A. Currently available results shows that anaerobic PMNs have substantial antimicrobial capacity. Whether this capacity is due to the O2-independent mechanisms discussed in this chapter remains to be established with greater certainty.