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Activation of murine peritoneal macrophages by Streptococcus pneumoniae type II capsular polysaccharide: involvement
1Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Suwon city, Kyunggi-do, 440-746 South Korea.
Abstract:
In this study we examined the ability of capsular polysaccharide type 2 (PS) from Streptococcus pnemoniae to induce secretory and cellular responses in peritoneal macrophages. Tumour cytotoxicity induced by preincubation with PS was demonstrated to be concentration-dependent. PS-induced tumouricidal activity was partially abrogated by anti-tumour necrosis factor (TNF)-alpha and inhibitor of nitric oxide, whereas anti-interferon (IFN)-alpha/beta antibody and the scavengers of reactive oxygen intermediates had no effect. In addition, supernatants from macrophages treated with PS contained TNF-alpha, and their iNOS-enzymatic activity was significantly increased. Thus, the tumouricidal activity induced by PS appeared to be mediated by the production of TNF-alpha and nitrite. Treatment of macrophages with PS increased the expression of CD14, the receptor for lipolysaccharide (LPS)/LPS-binding protein. Moreover, blocking antibody to CD14 abrogated partially TNF-alpha and nitrite induction by PS, suggesting that the PS-induced CD14 upregulation was correlated with secretion of TNF-alpha and nitrite. Taken together, these results demonstrate that PS may induce macrophage-secretory and cellular activities, in part, possibly via CD14-dependent pathway.
Insights
Capsular polysaccharide type 2 from Streptococcus pneumoniae activates macrophages to fight tumors. This immune response involves tumor necrosis factor-alpha and nitric oxide production, potentially through the CD14 receptor.
Area of Science:
- Immunology
- Microbiology
Background:
- Macrophages are key immune cells involved in tumor surveillance.
- Streptococcus pneumoniae capsular polysaccharide (PS) is a critical virulence factor.
- Understanding how bacterial components modulate macrophage function is vital for developing immunotherapies.
Purpose of the Study:
- To investigate the capacity of capsular polysaccharide type 2 (PS) from Streptococcus pneumoniae to stimulate peritoneal macrophages.
- To elucidate the mechanisms underlying PS-induced macrophage-mediated tumor cytotoxicity.
Main Methods:
- Peritoneal macrophages were incubated with varying concentrations of PS.
- Tumor cytotoxicity was assessed.
- Levels of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) were measured.
- Expression of CD14 was analyzed.
- Blocking antibodies against CD14, TNF-alpha, and interferon (IFN)-alpha/beta were used.
Main Results:
- PS induced concentration-dependent tumor cytotoxicity in macrophages.
- Tumoricidal activity was partially dependent on TNF-alpha and NO production.
- PS treatment increased TNF-alpha secretion and inducible nitric oxide synthase (iNOS) activity.
- PS upregulated CD14 expression on macrophages.
- Blocking CD14 partially inhibited TNF-alpha and nitrite induction.
Conclusions:
- Capsular polysaccharide type 2 from Streptococcus pneumoniae activates macrophages to exhibit tumoricidal activity.
- This activity is mediated by the production of TNF-alpha and nitrite.
- The CD14 receptor may play a role in PS-induced macrophage activation and effector functions.