TY - JOUR
T1 - Fungal β-glucan interacts with vitronectin and stimulates tumor necrosis factor alpha release from macrophages
AU - Olson, Eric J.
AU - Standing, Joseph E.
AU - Griego-Harper, Natalie
AU - Hoffman, Orleen A.
AU - Limper, Andrew H.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1128/iai.64.9.3548-3554.1996
DO - 10.1128/iai.64.9.3548-3554.1996
M3 - Article
C2 - 8751898
AN - SCOPUS:0029849098
SN - 0019-9567
VL - 64
SP - 3548
EP - 3554
JO - Infection and Immunity
JF - Infection and Immunity
IS - 9
ER -