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Macrophage activation and generation of tumoricidal activity by liposome-associated human C-reactive protein
Abstract:
The effect of human C-reactive protein incorporated into multilamellar vesicles (CRP-MLV) was studied in assays of macrophage function. Peritoneal exudate macrophages from C57BL/6 mice phagocytosed CRP-MLV in vitro more rapidly than multilamellar vesicles bearing comparable amounts of immunoglobulin G. Exposure of peritoneal exudate macrophages in vitro to CRP-MLV resulted in development of tumoricidal activity against syngeneic T241 fibrosarcoma and B-16 melanoma cells and against allogeneic Sarcoma 1 cells. Peritoneal exudate macrophages obtained from mice given CRP-MLV i.p. demonstrated antitumor activity against the syngeneic T241 fibrosarcoma in a Winn-type assay, and when challenged in vitro with phorbol myristate acetate, they showed elevated superoxide anion production. Administration of CRP-MLV i.p. did not enhance natural killer activity of spleen cells, however. In superoxide anion assays, CRP-MLV were approximately 10 to 100 times more effective than free C-reactive protein. Results indicate that C-reactive protein is capable of activating macrophages, thus supporting the concept of C-reactive protein as an immunomodulator.
Insights
Human C-reactive protein (CRP) incorporated into multilamellar vesicles (CRP-MLV) effectively activates macrophages. This activation leads to enhanced phagocytosis and tumoricidal activity, supporting CRP's role as an immunomodulator.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- C-reactive protein (CRP) is a key acute-phase protein.
- Its role in innate immunity and macrophage activation is under investigation.
- Multilamellar vesicles (MLVs) are used as delivery systems.
Purpose of the Study:
- To investigate the effect of human CRP incorporated into MLVs (CRP-MLV) on macrophage function.
- To assess CRP-MLV's ability to induce macrophage activation and antitumor activity.
- To compare the efficacy of CRP-MLV with free CRP and immunoglobulin G (IgG)-coated MLVs.
Main Methods:
- In vitro assays using peritoneal exudate macrophages from C57BL/6 mice.
- Phagocytosis assays comparing CRP-MLV with IgG-MLV.
- In vitro and in vivo (Winn-type assay) assessment of tumoricidal activity against various cancer cell lines.
- Measurement of superoxide anion production in macrophages stimulated with phorbol myristate acetate.
- Assessment of natural killer (NK) cell activity in spleen cells.
Main Results:
- Macrophages phagocytosed CRP-MLV more rapidly than IgG-MLV.
- Exposure to CRP-MLV induced tumoricidal activity against syngeneic and allogeneic tumor cells.
- In vivo administration of CRP-MLV enhanced antitumor activity and macrophage superoxide anion production.
- CRP-MLV were 10-100 times more potent than free CRP in superoxide anion assays.
- CRP-MLV did not enhance NK cell activity.
Conclusions:
- C-reactive protein incorporated into multilamellar vesicles is a potent activator of macrophages.
- CRP-MLV demonstrates significant antitumor activity, mediated by activated macrophages.
- These findings support the concept of C-reactive protein as a potential immunomodulator for therapeutic applications.