Fungal beta-glucan interacts with vitronectin and stimulates tumor necrosis factor alpha release from macrophages.
beta-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 beta-glucan receptors, thereby inducing release of tumor necrosis factor alpha (TNF-alpha). 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 beta-glucans and subsequently augments macrophage TNF-alpha release in response to this fungal component. To study this, we first determined the release of TNF-alpha from alveolar macrophages stimulated with fungal beta-glucan. Maximal TNF-alpha release occurred with moderate concentrations of beta-glucan (100 to 200 micrograms/ml), whereas higher concentrations of beta-glucan (> or = 500 micrograms/ml) caused apparent suppression of the TNF-alpha activity released. This suppression of TNF-alpha activity by high concentrations of beta-glucan was mediated by the particulate beta-glucan binding soluble TNF-alpha, through the lectin-binding domain of the cytokine, rendering the TNF-alpha less available for measurement. Next, we assessed the interaction of vitronectin with beta-glucan. Binding of 125I-vitronectin to particulate fungal beta-glucan was dose dependent and specifically inhibitable by unlabeled vitronectin. Furthermore, treatment of beta-glucan with vitronectin substantially augmented macrophage TNF-alpha release in response to this fungal component. These findings demonstrate that fungal beta-glucan can directly modulate TNF-alpha release from macrophages. Further, these studies indicate that the host adhesive glycoprotein vitronectin specifically binds beta-glucan and augments macrophage cytokine release in response to this fungal element.
Olson
E J
EJ
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Standing
J E
JE
Griego-Harper
N
N
Hoffman
O A
OA
Limper
A H
AH
D000818:Animals; D002473:Cell Wall / Q000276:immunology*; D005936:Glucans / Q000276:immunology*; D037102:Lectins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism*
D005936:Glucans; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; D019096:Vitronectin