Fungal β-glucan interacts with vitronectin and stimulates tumor necrosis factor alpha release from macrophages

Eric J. Olson, Joseph E. Standing, Natalie Griego-Harper, Orleen A. Hoffman, Andrew H. Limper

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

β-Glucans are polymers of D-glucose which represent major structural components of fungal cell walls. It was shown previously that fungi interact with macrophages through β-glucan receptors, thereby inducing release of tumor necrosis factor alpha (TNF-α). Additional studies demonstrated that vitronectin, a host adhesive glycoprotein, binds to fungi and enhances macrophage recognition of these organisms. Since vitronectin contains a carbohydrate-binding region, we postulated that vitronectin binds fungal β- glucans and subsequently augments macrophage TNF-α release in response to this fungal component. To study this, we first determined the release of TNF- α from alveolar macrophages stimulated with fungal β-glucan. Maximal TNF- α release occurred with moderate concentrations of β-glucan (100 to 200 μg/ml), whereas higher concentrations of β-glucan (≤500 μg/ml) caused apparent suppression of the TNF-α activity released. This suppression of TNF-α activity by high concentrations of β-glucan was mediated by the particulate β-glucan binding soluble TNF-α, through the lectin-binding domain of the cytokine, rendering the TNF-α less available for measurement. Next, we assessed the interaction of vitronectin with β-glucan. Binding of 125I-vitronectin to particulate fungal β-glucan was dose dependent and specifically inhibitable by unlabeled vitronectin. Furthermore, treatment of β-glucan with vitronectin substantially augmented macrophage TNF-α release in response to this fungal component. These findings demonstrate that fungal β-glucan can directly modulate TNF-α release from macrophages. Further, these studies indicate that the host adhesive glycoprotein vitronectin specifically binds β-glucan and augments macrophage cytokine release in response to this fungal element.

Original languageEnglish (US)
Pages (from-to)3548-3554
Number of pages7
JournalInfection and Immunity
Volume64
Issue number9
StatePublished - Sep 22 1996

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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