Inhibition of specific amino acid uptake in Candida albicans by lysosomal extracts from rabbit alveolar macrophages

Peterson, Elisabeth; Calderone, R A

doi:10.1128/iai.21.2.506-513.1978

Cited by 19 publications

(9 citation statements)

References 23 publications

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“…Leukocyte cationic proteins and other granule-associated substances have known antifungal properties (14,16,19) and may also enhance the activity of oxidative mechanisms (17). However, polyanions did not inhibit monocyte-medi-ated damage to Rhizopus hyphae, in contrast to our previous results for neutrophil-mediated damage to these fungi (6).…”

Section: Discussioncontrasting

confidence: 94%

Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro

Diamond¹,

Haudenschild²,

Erickson³

1982

Infect Immun

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Clinicopathological correlations from human cases and experimental animal studies suggest that neutrophils are critical components of the host response to mucormycosis but that other cellular defense mechanisms appear to be important as well. Since our previous studies demonstrated that Rhizoplus olyzae hyphae which are too large to be ingested completely can be damaged and probably killed by human neutrophils, we studied the antihyphal activity of human monocytes. As with neutrophils, light and electron microscopic studies indicated that monocytes attached to hyphae and appeared to destroy them in the absence of serum. As judged by our previously described assay for the leukocyte-induced inhibition of [14C]uracil uptake by hyphae, quantitative damage to hyphae by monocytes was 40.8 ± 2.2% in 54 experiments. Neither attachment to nor damage of hyphae by monocytes was augmented by the presence of 10% human serum. As with neutrophils, monocyte-mediated damage of R. orvzae was significantly decreased by some inhibitors of oxidative metabolism and scavengers of the potentially microbicidal oxidative leukocyte products, which included 10-4 M sodium azide, 10-3 M sodium cyanide, catalase, 10-3 M histidine, 10-3 M tryptophan, and 10-4 M 1,4-diazobicyclo[2.2.2]octane but not superoxide dismutase, 1.4 x 10-2 M dimethyl sulfoxide, and 4.0 x 10-1 M mannitol. Moreover, monocytes from three patients with chronic granulomatous disease failed to damage hyphae at all. In contrast to our previous data for neutrophils, polyanions (10-5 M polyaspartic or polyglutamic acid) did not inhibit monocyte-mediated hyphal damage. Thus, monocytes can damage and probably kill R. orvlzae hyphae by oxidative mechanisms and so may be involved in host defense mechanisms against mucormycosis.

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Section: Discussioncontrasting

confidence: 94%

Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro

Diamond¹,

Haudenschild²,

Erickson³

1982

Infect Immun

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“…Of the amino acids thus far examined (leucine, methionine, lysine, proline and glutamate) significant levels of uptake were detectable only for proline and glutamate. While these findings seemed surprising, lysosomal extracts inhibited uptake of lysine, valine, leucine, methionine and phenylalanine, but not of glutamate or proline in Cundida albicans (Peterson & Calderone, 1978). Thus, the transport and utilization of glutamate and proline could be important to survival in the lysosomal environment.…”

Section: Introductionmentioning

confidence: 94%

Active Transport of Proline by Coxiella burnetii

Hendrix

Mallavia

1984

Microbiology

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The obligate intracellular rickettsia, Coxiella burnetii, was shown to possess an energy dependent proline transport system which displayed a high degree of specificity and was highly dependent on pH. Transport was maximal at pH 3.0 to 4.5, a pH range approximately that of the host cell phagolysosome where the agent replicates. Transport was inhibited by the uncouplers carbonyl cyanide m-chlorophenylhydrazone and dinitrophenol, but not by sodium arsenite. In the presence of glutamate, a preferred energy source, proline uptake was enhanced more than two-fold. This enhancement of proline uptake was greatly decreased in the presence of sodium arsenite. The addition of glutamate decreased the apparent Km for proline transport from 45 microM to 15 microM, with the Vmax increasing from 3.6 pmol s-1 (mg dry wt)-1 to 4.8 pmol s-1 (mg dry wt)-1. Two proline analogues, furoic acid and azetidine-2-carboxylic acid, were effective inhibitors of proline transport. D-Proline, 4-hydroxyproline, glycine and proline amide inhibited transport minimally, while no inhibition was seen with succinate, pyruvate or glutamate.

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“…Peterson and Calderone have recently reported low levels of antifungal activity (7,37) in extracts from frozen and thawed granules of rabbit alveolar macrophages. Although it is possible that they were detecting the biological activity of the microbicidal cationic proteins described herein, we have found freeze-thawing to be an ineffective means of releasing macrophage cationic proteins from their cellular organelle(s).…”

Section: Sucrose)mentioning

confidence: 99%

Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism

Patterson-Delafield¹,

Martínez²,

Lehrer³

1980

Infect Immun

143

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Rabbit alveolar macrophages contain two highly cationic microbicidal proteins. These were shown to be distinct from histones and not to arise from granulocyte contamination. The macrophage proteins were especially active against Candida albicans and Candida parapsilosis. Gram-positive bacteria (Bacillus subtilis, Listeria monocytogenes, and Streptococcus faecalis) were also susceptible, whereas Escherichia coli and Salmonella typhimurium appeared more resistant. The proteins may be present in lysosomes, based on their solubilization by dilute acids and their distribution with lysosomal markers on sucrose density gradients. Such microbicidal proteins have not previously been demonstrated in any mammalian macrophage. They may play a significant role in the host-defense functions of the rabbit lung. The function of alveolar macrophages in host defense is well documented, and numerous reports describe their microbicidal proficiency (recently reviewed by Hocking and Golde [21]). Relatively little is known concerning the microbicidal mechanisms used by alveolar macrophages (4, 23). Recent studies in our laboratory (26) demonstrated that the mechanism(s) whereby rabbit alveolar macrophages killed Candida albicans differed substantially from the myeloperoxidase-H202-mediated antifungal systems predominantly operative in human monocytes (24) and neutrophils (25). Rabbit granulocytes have been shown to contain microbicidal lysosomal cationic proteins (41-43), certain of which kill C. albicans (27). As macrophages and granulocytes are thought to arise from a common stem cell (21), and as these cells contain certain constituents in common (e.g., lysozyme), we sought the presence of microbicidal cationic proteins with candidacidal activity in rabbit alveolar macrophages. This communication describes our findings. MATERIALS AND METHODS Cell preparations and fractionation. (i) Isolation of pulmonary macrophages. Macrophages were obtained by ravaging the airways of 2-to 3-kg New Zealand white rabbits according to the procedure of Myrvik (34) with the following modifications: (i) the lungs were ravaged in situ after the animal had been sacrificed by intravenous injection of 180 mg of sodium

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Inhibition of specific amino acid uptake in Candida albicans by lysosomal extracts from rabbit alveolar macrophages

Cited by 19 publications

References 23 publications

Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro

Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro

Active Transport of Proline by Coxiella burnetii

Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism

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