Vitronectin and fibronectin function as glucan binding proteins augmenting macrophage responses to Pneumocystis carinii

Robert Vassallo, T. J. Kottom, J. E. Standing, Andrew Harold Limper

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

β-glucans represent major structural components of fungal cell walls. We recently reported that Pneumocystis carinii β-glucans stimulate alveolar macrophages to release proinflammatory cytokines. Macrophage activation by β-glucan is augmented by serum, implying the presence of circulating factors that interact with β-glucans and enhance their ability to stimulate macrophages. Using β-glucan - enriched cell wall fractions from P. carinii and Saccharomyces cerevisiae, two prominent proteins were precipitated from serum and demonstrated to be vitronectin (VN) and fibronectin (FN) by immune analysis. Preincubation of β-glucan with VN or FN enhanced macrophage activation in response to this cell wall component. Because VN and FN accumulate in the lungs during P. carinii pneumonia, we further investigated hepatic and pulmonary expression of VN and FN messenger RNA during infection. P. carinii pneumonia in rodents is associated with increased hepatic expression of VN and FN as well as increased local expression of FN in the lung. Because interleukin (IL)-6 represents the major regulator of VN and FN expression during inflammatory conditions, we measured macrophage IL-6 release in response to stimulation with P. carinii β-glucan. Stimulation of macrophages with P. carinii β-glucan induced significant release of IL-6. Elevated concentrations of IL-6 were noted in the blood of infected animals compared with uninfected control animals. These studies indicate that VN and FN bind to β-glucan components of P. carinii and augment macrophage inflammatory responses. P. carinii cell wall β-glucan stimulates secretion of IL-6 by macrophages, thereby enhancing hepatic synthesis of both VN and FN, and lung synthesis of FN during pneumonia.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume25
Issue number2
StatePublished - 2001

Fingerprint

Vitronectin
Pneumocystis carinii
Glucans
Macrophages
Fibronectins
Interleukin-6
Cell Wall
Cells
Lung
Pneumocystis Pneumonia
Macrophage Activation
Liver
Animals
Chemical activation
Fungal Structures
glucan-binding proteins
Alveolar Macrophages
Cellular Structures
Serum
Yeast

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

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title = "Vitronectin and fibronectin function as glucan binding proteins augmenting macrophage responses to Pneumocystis carinii",
abstract = "β-glucans represent major structural components of fungal cell walls. We recently reported that Pneumocystis carinii β-glucans stimulate alveolar macrophages to release proinflammatory cytokines. Macrophage activation by β-glucan is augmented by serum, implying the presence of circulating factors that interact with β-glucans and enhance their ability to stimulate macrophages. Using β-glucan - enriched cell wall fractions from P. carinii and Saccharomyces cerevisiae, two prominent proteins were precipitated from serum and demonstrated to be vitronectin (VN) and fibronectin (FN) by immune analysis. Preincubation of β-glucan with VN or FN enhanced macrophage activation in response to this cell wall component. Because VN and FN accumulate in the lungs during P. carinii pneumonia, we further investigated hepatic and pulmonary expression of VN and FN messenger RNA during infection. P. carinii pneumonia in rodents is associated with increased hepatic expression of VN and FN as well as increased local expression of FN in the lung. Because interleukin (IL)-6 represents the major regulator of VN and FN expression during inflammatory conditions, we measured macrophage IL-6 release in response to stimulation with P. carinii β-glucan. Stimulation of macrophages with P. carinii β-glucan induced significant release of IL-6. Elevated concentrations of IL-6 were noted in the blood of infected animals compared with uninfected control animals. These studies indicate that VN and FN bind to β-glucan components of P. carinii and augment macrophage inflammatory responses. P. carinii cell wall β-glucan stimulates secretion of IL-6 by macrophages, thereby enhancing hepatic synthesis of both VN and FN, and lung synthesis of FN during pneumonia.",
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AU - Vassallo, Robert

AU - Kottom, T. J.

AU - Standing, J. E.

AU - Limper, Andrew Harold

PY - 2001

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N2 - β-glucans represent major structural components of fungal cell walls. We recently reported that Pneumocystis carinii β-glucans stimulate alveolar macrophages to release proinflammatory cytokines. Macrophage activation by β-glucan is augmented by serum, implying the presence of circulating factors that interact with β-glucans and enhance their ability to stimulate macrophages. Using β-glucan - enriched cell wall fractions from P. carinii and Saccharomyces cerevisiae, two prominent proteins were precipitated from serum and demonstrated to be vitronectin (VN) and fibronectin (FN) by immune analysis. Preincubation of β-glucan with VN or FN enhanced macrophage activation in response to this cell wall component. Because VN and FN accumulate in the lungs during P. carinii pneumonia, we further investigated hepatic and pulmonary expression of VN and FN messenger RNA during infection. P. carinii pneumonia in rodents is associated with increased hepatic expression of VN and FN as well as increased local expression of FN in the lung. Because interleukin (IL)-6 represents the major regulator of VN and FN expression during inflammatory conditions, we measured macrophage IL-6 release in response to stimulation with P. carinii β-glucan. Stimulation of macrophages with P. carinii β-glucan induced significant release of IL-6. Elevated concentrations of IL-6 were noted in the blood of infected animals compared with uninfected control animals. These studies indicate that VN and FN bind to β-glucan components of P. carinii and augment macrophage inflammatory responses. P. carinii cell wall β-glucan stimulates secretion of IL-6 by macrophages, thereby enhancing hepatic synthesis of both VN and FN, and lung synthesis of FN during pneumonia.

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