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Serum components induce beta-D-glucan-inhibitable uptake of zymosan particles by murine peritoneal macrophages
Abstract:
Effects of murine serum (NMS) treatment on (1-->3)-beta-D-glucan inhibitable uptake of zymosan particles (ZYM) (GIZUP) by murine peritoneal macrophages (PM) and the structural specificity of the inhibition were examined. ZYM uptake by PM treated with NMS was enhanced in comparison with those treated with medium, and in a concentration- and incubation time-dependent manner. The enhanced ZYM uptake was significantly reduced by the pretreatment of PM with soluble (1-->3)-beta-D-glucans. These facts suggest that NMS enhances GIZUP. The effect disappeared by the treatment of NMS with gelatin-Sepharose which removed fibronectin (FN) from the serum, suggesting a significant contribution of FN on GIZUP. In addition, the administration of beta-glucan in vivo elevated the concentration of FN in serum by acute phase response and enhanced GIZUP, suggesting the positive contribution of acute phase responses on beta-glucan mediated immunopharmacological activities. Of particular interest, the inhibition was shown by both antitumor active and inactive glucans. These facts suggested that the recognition of beta-glucans by PM, which would proceed at a relatively early period of whole activation pathways, would not be enough to fully activate the host to show antitumor activity.
Insights
Murine serum (NMS) enhances zymosan particle uptake by macrophages, a process mediated by fibronectin (FN). This suggests beta-glucan
Area of Science:
- Immunology
- Biochemistry
Background:
- Murine serum (NMS) affects the uptake of zymosan particles (ZYM) by peritoneal macrophages (PM).
- The (1-->3)-beta-D-glucan inhibitable uptake of zymosan particles (GIZUP) is a key process in macrophage function.
- Fibronectin (FN) is a component of murine serum that may influence GIZUP.
Purpose of the Study:
- To investigate the effects of NMS on GIZUP by murine PM.
- To determine the role of fibronectin (FN) in NMS-mediated enhancement of GIZUP.
- To explore the contribution of acute phase responses to beta-glucan-mediated immunopharmacological activities.
Main Methods:
- Treatment of murine peritoneal macrophages (PM) with murine serum (NMS) or medium.
- Measurement of zymosan particle (ZYM) uptake by PM.
- Pretreatment of PM with soluble (1-->3)-beta-D-glucans.
- Treatment of NMS with gelatin-Sepharose to remove fibronectin (FN).
- Administration of beta-glucan in vivo and measurement of serum FN concentration and GIZUP.
Main Results:
- NMS treatment enhanced ZYM uptake by PM in a concentration- and time-dependent manner.
- The enhanced ZYM uptake was reduced by pretreatment with soluble (1-->3)-beta-D-glucans.
- Removal of FN from NMS abolished the enhancement of GIZUP, indicating FN's significant contribution.
- In vivo administration of beta-glucan increased serum FN via acute phase response, enhancing GIZUP.
- Both antitumor active and inactive glucans inhibited GIZUP, suggesting early recognition is insufficient for full activation.
Conclusions:
- Murine serum (NMS) enhances (1-->3)-beta-D-glucan inhibitable uptake of zymosan particles (GIZUP) by murine peritoneal macrophages (PM).
- Fibronectin (FN) in NMS plays a significant role in enhancing GIZUP.
- Acute phase responses contribute positively to beta-glucan-mediated immunopharmacological activities.
- Early recognition of beta-glucans by PM is necessary but not sufficient for full host activation and antitumor activity.