Identification of constituents of human neutrophil azurophil granules that mediate fungistasis against Histoplasma capsulatum.
نویسندگان
چکیده
Previously we demonstrated that human neutrophils mediate potent and long-lasting fungistasis against Histoplasma capsulatum yeasts and that all of the fungistatic activity resides in the azurophil granules. In the present study, specific azurophil granule constituents with fungistatic activity were identified by incubation with H. capsulatum yeasts for 24 h and by quantifying the subsequent growth of yeasts via the incorporation of [(3)H]leucine. Human neutrophil defensins HNP-1, HNP-2, and HNP-3 inhibited the growth of H. capsulatum yeasts in a concentration-dependent manner with maximum inhibition at 8 microg/ml. At a concentration of 4 microg/ml, all possible paired combinations of defensins exhibited additive fungistatic activity against H. capsulatum yeasts. Cathepsin G and bactericidal-permeability-increasing protein (BPI) also mediated fungistasis against H. capsulatum in a concentration-dependent manner. The fungistatic activities of combinations of cathepsin G and BPI were additive, as were those of combinations of cathepsin G or BPI with HNP-1, HNP-2, and HNP-3. Lysozyme and elastase exhibited modest antifungal activity, and azurocidin and proteinase 3 exhibited no significant fungistasis against H. capsulatum yeasts. Thus, defensins, cathepsin G, and BPI are the major anti-H. capsulatum effector molecules in the azurophil granules of human neutrophils.
منابع مشابه
Human Neutrophil - mediated Fungistasis against Histoplasma capsulatum
Human neutrophils (PMN) demonstrated potent fungistatic activity against Histoplasma capsulatum (Hc) yeasts in a sensitive microassay that quantifies the growth of yeasts by the incorporation of 13Hjleucine. At a PMN:yeast ratio of 1:2, PMN inhibited the growth of yeasts by 37%. Maximum inhibition of85% to 95% was achieved at a PMN/yeast ratio of 10:1 to 50:1. Opsonization of the yeasts in fres...
متن کاملHistoplasma capsulatum Fungistatic/Fungicidal Activity against Phagosome Acidification to Mediate Human Macrophages Do Not Require
متن کامل
Biochemical and Morphological Characterization of Azurophil and Specific Granules of Human Neutrophilic Polymorphonuclear Leukocytes
Postnuclear supernates from homogenates of purified neutrophil polymorphonuclear leukocytes (PMNs) from human blood were fractionated by zonal sedimentation and isopycnic equilibration in sucrose gradients. The fractions were characterized biochemically by measuring protein content and the activities of eight enzymes. Selected fractions were further analyzed by electron microscopy. In both cent...
متن کاملMembrane Proteins in Human Neutrophils Identification and characterization of lipid rafts in subcellular organelles
The human neutrophil is an important effector cell in acute inflammation and in the innate immune response against bacteria and fungi. When immune reactions occur in the tissue in response to antigen challenge, neutrophils are the first cells to enter the site of inflammation. The neutrophil is equipped with a vast amount of receptors that both interact with inflammatory mediators and host tiss...
متن کاملIn situ localization by double-labeling immunoelectron microscopy of anti-neutrophil cytoplasmic autoantibodies in neutrophils and monocytes.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated with active Wegener's granulomatosis are directed against a soluble 29-Kd protein present in human neutrophils and monocytes. Affinity labeling with tritiated diisopropylfluorophosphate (3H-DFP) suggested that ANCA-antigen is a serine protease. We used immunoelectron microscopy to study the in situ localization of the ANCA-antigen in ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Infection and immunity
دوره 68 10 شماره
صفحات -
تاریخ انتشار 2000