CYTOPLASTS GENERATE OXIDANTS BUT REQUIRE ADDED NEUTROPHIL GRANULE CONSTITUENTS FOR FUNGICIDAL ACTIVITY AGAINST CANDIDA-ALBICANS HYPHAE

Killing of Candida albicans hyphae requires oxidant generation by neut rophils (PMNL), but it is uncertain whether hyphal killing is mediated by PMNL oxidants alone or requires contributions by granule constitue nts. This was assessed using U-cytoplasts (U-CYT), anucleate PMNL frag ments depleted of cytoplasmic granules but retaining motility and resp iratory burst activity, Granule-depleted U-CYT killed Staphylococcus a ureus, but hyphae remained viable despite targeted generation of putat ively fungicidal oxidants by avidly adherent U-CYT, Hyphal killing occ urred by combining U-CYT with sublethal concentrations of purified PMN L granule extracts approximating those present in equivalent numbers o f intact PMNL, Contributions of granule constituents were not entirely attributable to purified granule constituents with known antimicrobia l activity (lactoferrin, cathepsin G, myeloperoxidase, and human neutr ophil peptide defensins 1-3) individually or combined, Thus, oxidant g eneration by intact PMNL may be necessary but not always sufficient to mediate hyphal killing without complementary nonoxidative mechanisms.