Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis

Journal Article · Mon Jul 01 00:00:00 EDT 1991 · Infection and Immunity; (United States)

OSTI ID:5590548

Alspaugh, J A; Granger, D L ^[1]

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1. Department of Medicine, Duke University School of Medicine, Durham, NC (USA)

Activated macrophages are able to inhibit the replication of intracellular microbes and tumor cells. In the murine system, this cytostatic effect is associated with the oxidation of L-arginine to L-citrulline, nitrite, and nitrate and is thought to be mediated by an intermediate of this reaction, possibly nitric oxide (NO.). By exposing replicating Cryptococcus neoformans cells to conditions under which NO. is chemically generated, we have observed a cytostatic effect similar to that caused by activated murine macrophages. Nitric oxide is formed as a decomposition product of nitrite salts in acidic, aqueous solutions. Although C. neoformans replicates well in the presence of high nitrite concentrations at physiologic pH, its growth in acidic media can be inhibited by the addition of low concentrations of sodium nitrite. The degree of cytostasis is dependent on both the pH and the nitrite concentration of the NO. generating solution. The cytostatic effector molecule appears to be a gas since, in addition to inhibiting C. neoformans replication in solution, it is able to exert its inhibitory effect across a gas-permeable but ion-impermeable membrane. At high nitrite concentrations, a fungicidal effect occurs. We propose that the growth inhibition of C. neoformans upon exposure to chemically generated NO. or some related oxide of nitrogen represents a cell-free system simulating the cytostatic effect of activated murine macrophages.

• OSTI ID: 5590548
• Journal Information: Infection and Immunity; (United States), Vol. 59:7; ISSN 0019-9567
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
MACROPHAGES
BIOLOGICAL FUNCTIONS
NITROGEN OXIDES
BIOLOGICAL EFFECTS
YEASTS
GROWTH
GLUCOSE
IN VITRO
INHIBITION
METABOLISM
NITRIC OXIDE
RADICALS
ALDEHYDES
ANIMAL CELLS
CARBOHYDRATES
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
EUMYCOTA
FUNGI
HEXOSES
MICROORGANISMS
MONOSACCHARIDES
NITROGEN COMPOUNDS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
PLANTS
SACCHARIDES
SOMATIC CELLS
560300* - Chemicals Metabolism & Toxicology