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Polyanions inhibit murine macrophage Fc receptor mediated ADCC and binding
R Mocharla1, H Mocharla, R W Leu
1Department of Medical Genetics, School of Medicine, Indiana University, Indianapolis 46223.
Abstract:
We examined the effect of various polyanions on mouse complement hemolytic activity, Fc receptor (FcR) subclass mediated antibody-dependent cellular cytotoxicity (ADCC) as well as binding by mouse peritoneal macrophages (M phi) of sheep erythrocyte targets. All the polyanions tested (dextran sulfate, carrageenan, polyvinyl sulfate, pentosan polysulfate and polyanethol sulfonic acid) inhibited the hemolytic activity of mouse serum complement to varying degrees. Polyanions inhibited ADCC mediated by either IgG2a or IgG2b in a reversible manner. FcR subclass mediated binding studies at 4 degrees C indicated that the various polyanions compete for FcR binding of sheep erythrocytes opsonized with murine IgG2a, IgG2b and polyclonal IgG. Polyanethol sulfonic acid was uniformly the most potent inhibitor of mouse CH50 and FcR dependent ADCC and binding functions, but did not affect C3b receptor mediated binding.
Insights
Various polyanions inhibit mouse complement activity and Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC). Polyanethol sulfonic acid showed the strongest inhibitory effect on complement hemolytic activity and FcR-dependent functions.
Area of Science:
- Immunology
- Biochemistry
Background:
- Complement system and Fc receptors (FcRs) are crucial for innate and adaptive immunity.
- Antibody-dependent cellular cytotoxicity (ADCC) is a key immune mechanism mediated by FcRs.
Purpose of the Study:
- To investigate the impact of different polyanions on mouse complement hemolytic activity.
- To evaluate the effect of polyanions on Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC).
- To determine polyanion interactions with FcR subclass-mediated binding of opsonized targets.
Main Methods:
- Assessed mouse serum complement hemolytic activity (CH50) in the presence of various polyanions.
- Measured Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC) using IgG2a and IgG2b subclasses.
- Conducted FcR subclass-mediated binding assays at 4°C with opsonized sheep erythrocytes.
Main Results:
- All tested polyanions (dextran sulfate, carrageenan, polyvinyl sulfate, pentosan polysulfate, polyanethol sulfonic acid) inhibited mouse complement hemolytic activity to varying extents.
- Polyanions reversibly inhibited ADCC mediated by IgG2a and IgG2b.
- Polyanions competed for FcR binding of IgG-opsonized sheep erythrocytes, with polyanethol sulfonic acid being the most potent inhibitor.
- Polyanethol sulfonic acid did not affect C3b receptor-mediated binding.
Conclusions:
- Polyanions broadly inhibit mouse complement hemolytic activity and Fc receptor (FcR)-mediated functions, including ADCC and target binding.
- Polyanethol sulfonic acid exhibits the most significant inhibitory effect on complement and FcR-dependent immune responses.
- These findings highlight the potential of polyanions as modulators of complement and FcR-mediated immunity.