Takefumi Nikaido1, Yoshinori Tanino1, Xintao Wang1, Suguru Sato1, Kenichi Misa1, Naoko Fukuhara1, Yuki Sato1, Atsuro Fukuhara1, Manabu Uematsu1, Yasuhito Suzuki1, Tetsuhito Kojima2, Mishie Tanino3, Yuichi Endo4, Kohsuke Tsuchiya5, Ikuo Kawamura5, Charles W Frevert6, Mitsuru Munakata1. 1. Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima. 2. Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya. 3. Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo. 4. Department of Immunology, Fukushima Medical University School of Medicine, Fukushima. 5. Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 6. Division of Pulmonary/Critical Care Medicine, Department of Medicine Comparative Pathology Program, Department of Comparative Medicine Center of Lung Biology, University of Washington School of Medicine, Seattle.
Abstract
BACKGROUND: Syndecan-4 is a transmembrane heparan sulfate proteoglycan expressed in a variety of cells, and glycosaminoglycan side chains of syndecan-4 bind to several proteins, suggesting several biological functions. However, the role of syndecan-4 in acute bacterial pneumonia has not yet been elucidated. METHODS: Serum syndecan-4 levels were measured in patients with acute pneumonia, and the relationships between serum syndecan-4 levels and clinical parameters were analyzed. Next, we treated wild-type and syndecan-4-deficient mice with Streptococcus pneumoniae intranasally and analyzed the phenotype of syndecan-4-deficient mice. RESULTS: In the patients with acute pneumonia, serum syndecan-4 levels were significantly higher than in the healthy volunteers and correlated negatively with the pneumonia severity score. In addition, in patients who improved with short-term antibiotic therapy, serum syndecan-4 levels were higher on admission and gradually increased during antibiotic therapy. Furthermore, in syndecan-4-deficient mice, the survival rate was significantly worse, and total neutrophil counts in bronchoalveolar lavage fluid, bacterial counts in blood, and plasma levels of inflammatory cytokines were significantly higher than in wild-type mice. CONCLUSIONS: These results suggest that syndecan-4 has an anti-inflammatory function in acute pneumonia and could serve as a useful biomarker in these patients.
BACKGROUND:Syndecan-4 is a transmembrane heparan sulfate proteoglycan expressed in a variety of cells, and glycosaminoglycan side chains of syndecan-4 bind to several proteins, suggesting several biological functions. However, the role of syndecan-4 in acute bacterial pneumonia has not yet been elucidated. METHODS: Serum syndecan-4 levels were measured in patients with acute pneumonia, and the relationships between serum syndecan-4 levels and clinical parameters were analyzed. Next, we treated wild-type and syndecan-4-deficient mice with Streptococcus pneumoniae intranasally and analyzed the phenotype of syndecan-4-deficient mice. RESULTS: In the patients with acute pneumonia, serum syndecan-4 levels were significantly higher than in the healthy volunteers and correlated negatively with the pneumonia severity score. In addition, in patients who improved with short-term antibiotic therapy, serum syndecan-4 levels were higher on admission and gradually increased during antibiotic therapy. Furthermore, in syndecan-4-deficient mice, the survival rate was significantly worse, and total neutrophil counts in bronchoalveolar lavage fluid, bacterial counts in blood, and plasma levels of inflammatory cytokines were significantly higher than in wild-type mice. CONCLUSIONS: These results suggest that syndecan-4 has an anti-inflammatory function in acute pneumonia and could serve as a useful biomarker in these patients.