Damage to Pseudohyphal Forms of Candida albicans by Neutrophils in the Absence of Serum In Vitro

Diamond, Richard D.; Krzesicki, Raymond F.; Jao, Wellington

doi:10.1172/jci108945

Cited by 181 publications

(105 citation statements)

References 38 publications

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“…Lysozyme is also present in specific granules of neutrophils and was released in significant amounts from neutrophils during damage to Candida pseudohyphae (2). The results of our current experiments are comparable to those of other workers who used yeasts (21), i.e.…”

Section: Discussionsupporting

confidence: 90%

“…From our previous studies, this included activation of the myeloperoxidase-hydrogen peroxide-halide system (2), as evidenced by iodination of pseudohyphae by neutrophils, and chemiluminescence by neutrophils (16). However, the process was accompanied by only minimal release of lysosomal enzymes from the azurophil granules, which also contain myeloperoxidase (2). Nevertheless, the present experiments indicated that oxidative mechanisms of neutrophils were of central importance in damage to Candida pseudohyphae by neutrophils.…”

Section: Discussionmentioning

confidence: 53%

“…It is apparent that a defect in damage to pseudohyphae might occur due to a variety of factors, including inhibitory factors in serum, changes in the surface properties of neutrophils or pseudohyphae, defects in microtubules or microfilaments of neutrophils (2), and defects in neutrophil oxidative metabolism. The relative biological importance of these factors will have to be determined in future studies of patients with systemic candidiasis.…”

Section: Discussionmentioning

confidence: 99%

“…In earlier studies, we demonstrated that human peripheral blood neutrophils could completely ingest, and probably kill Candida albicans pseudohyphae in vitro (2). There appeared to be receptors on the neutrophil surface which directly recognized Candida pseudohyphae, without opsonization of Candida by specific antibody or by complement components and triggered leukocyte microbicidal mechanisms.…”

Section: Introductionmentioning

confidence: 85%

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Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

Daimond¹,

Krzesicki²

1978

J. Clin. Invest.

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121

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A B S T R A C T Mechanisms were studied that might explain the attachment and damage to Candida albicans pseudohyphae by neutrophils in the absence of serum. Attachment of neutrophils to pseudo hyphae was inhibited by Candida mannans (1-10 mg/ml), but not by mannose, dextran, chitin, conconavalin A, or highly charged polyamino acids. Contact was also inhibited by pretreatment of Candida before incubation with neutrophils with chymotrypsin, but not trypsin or several inhibitors of proteases. Similar results were obtained with pretreatment of neutrophils, except that trypsin was inhibitory. When pseudohyphae were killed with ultraviolet light, proteinpolysaccharide complexes of mol wt <10,000 were released which appeared to bind to the surfaces of neutrophils and inhibit contact between neutrophils and Candida, as well as other fungi.Damage to Candida by neutrophils was inhibited by agents known to act on neutrophil oxidative microbicidal mechanisms, including sodium cyanide, sodium azide, catalase, superoxide dismutase, and 1, 4 diazobicyclo (2, 2, 2) octane, a singlet oxygen quencher. Neutrophils from a patient with chronic granulomatous disease did not damage Candida at all. However, the hydroxyl radical scavengers mannitol and benzoate were not inhibitory. Cationic proteins and lactoferrin also did not appear to play a major role in this system. Low concentrations of lysozyme which Preliminary findings were presented in part at the Annual

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

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Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

Daimond¹,

Krzesicki²

1978

J. Clin. Invest.

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121

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“…These included glucose oxidase, in the presence ofglucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence ofmyeloperoxi- INTRODUCTION In previous studies in our laboratory, it was established that pseudohyphal and hyphal forms of Candida albicans could be damaged and probably killed by nonphagocytic mechanisms of human neutrophils in vitro (1). Experimental data indicated that Candida hyphae, though too large to be ingested, activated microbicidal mechanisms of neutrophils and caused specific release of neutrophil lysosomal enzymes (2).…”

mentioning

confidence: 99%

Damage to Candida albicans Hyphae and Pseudohyphae by the Myeloperoxidase System and Oxidative Products of Neutrophil Metabolism In Vitro

1980

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A B S T R A C T In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygendependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [14C]cytosine uptake. Neu-trophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance ofoxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae.Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence ofglucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence ofmyeloperoxi-

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Viability Assessment by Dye Exclusion

Auger¹

1979

Arch Dermatol

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Damage to Pseudohyphal Forms of Candida albicans by Neutrophils in the Absence of Serum In Vitro

Cited by 181 publications

References 38 publications

Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

Damage to Candida albicans Hyphae and Pseudohyphae by the Myeloperoxidase System and Oxidative Products of Neutrophil Metabolism In Vitro

Viability Assessment by Dye Exclusion

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