Document 0098
 DOCN  M9460098
 TI    Production of tumor necrosis factor alpha in human leukocytes stimulated
       by Cryptococcus neoformans.
 DT    9408
 AU    Levitz SM; Tabuni A; Kornfeld H; Reardon CC; Golenbock DT; Evans
       Memorial Department of Clinical Research, Boston University; Medical
       Center Hospital, Massachusetts 02118.
 SO    Infect Immun. 1994 May;62(5):1975-81. Unique Identifier : AIDSLINE
       MED/94222571
 AB    Tumor necrosis factor alpha (TNF-alpha) is a key mediator of
       inflammation and may promote human immunodeficiency virus replication in
       latently infected cells. Since cryptococcosis often is associated with
       aberrations in the host inflammatory response and occurs preferentially
       in persons with AIDS, we defined the conditions under which human
       leukocytes produce TNF-alpha when stimulated by Cryptococcus neoformans.
       Peripheral blood mononuclear cells (PBMC) produced comparable amounts of
       TNF-alpha following stimulation with C. neoformans and
       lipopolysaccharide. Detectable TNF-alpha release in response to C.
       neoformans occurred only when fungi with small-sized capsules were used
       and complement-sufficient serum was added. Fractionation of PBMC
       established that monocytes were the predominant source of TNF-alpha.
       TNF-alpha gene expression and release occurred significantly later in
       PBMC stimulated with C. neoformans than in PBMC stimulated with LPS. C.
       neoformans was also a potent inducer of TNF-alpha from freshly isolated
       bronchoalveolar macrophages (BAM). Upon in vitro culture, BAM and
       monocytes bound greater numbers of fungal cells, yet their capacity to
       produce TNF-alpha following cryptococcal stimulation declined by 74 to
       100%. However, this decline was reversed if the BAM and monocytes were
       cultured with gamma interferon. These data establish that C. neoformans
       can potently stimulate TNF-alpha release from human leukocytes. However,
       several variables profoundly affected the amount of TNF-alpha released,
       including the type of leukocyte and its state of activation, the size of
       the cryptococcal capsule, and the availability of opsonins.
 DE    Cryptococcus neoformans/GROWTH & DEVELOPMENT/*PATHOGENICITY  Gene
       Expression  Human  Interferon Type II/PHARMACOLOGY
       Leukocytes/*METABOLISM  Phagocytosis  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Tumor Necrosis Factor/*BIOSYNTHESIS/GENETICS
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).