title: Cytoplasts generate oxidants but require added neutrophil granule constituents for fungicidal activity against Candida albicans hyphae.
abstract: Killing of Candida albicans hyphae requires oxidant generation by neutrophils (PMNL), but it is uncertain whether hyphal killing is mediated by PMNL oxidants alone or requires contributions by granule constituents. This was assessed using U-cytoplasts (U-CYT), anucleate PMNL fragments depleted of cytoplasmic granules but retaining motility and respiratory burst activity. Granule-depleted U-CYT killed Staphylococcus aureus, but hyphae remained viable despite targeted generation of putatively fungicidal oxidants by avidly adherent U-CYT. Hyphal killing occurred by combining U-CYT with sublethal concentrations of purified PMNL granule extracts approximating those present in equivalent numbers of intact PMNL. Contributions of granule constituents were not entirely attributable to purified granule constituents with known antimicrobial activity (lactoferrin, cathepsin G, myeloperoxidase, and human neutrophil peptide defensins 1-3) individually or combined. Thus, oxidant generation by intact PMNL may be necessary but not always sufficient to mediate hyphal killing without complementary nonoxidative mechanisms.
authors.affiliation: Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, Massachusetts, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Stein
authors.forename: S E
authors.initials: SE
authors.lastname: Malawista
authors.forename: G
authors.initials: G
authors.lastname: Van Blaricom
authors.forename: D
authors.initials: D
authors.lastname: Wysong
authors.forename: R D
authors.initials: RD
authors.lastname: Diamond
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D009195:Peroxidase / Q000494:pharmacology; D010587:Phagocytosis; D016897:Respiratory Burst / Q000187:drug effects; D012697:Serine Endopeptidases
chemical_list: D009895:Opsonin Proteins; D016877:Oxidants; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D002403:Cathepsins; D007781:Lactoferrin; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G