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Effect of heparin on the reactivity of SH-groups in the macrophage membrane
Abstract:
The effect of heparin on macrophage (M phi) adherence and on the reactivity of membrane SH-groups to the specific SH-oxidizing agent 4,4'-dithiodipyridine (PDS) was studied. Various types of SH-reactive agents, except 5,5'-dithio-bis (2-nitrobenzoate) (DTNB), were found to inhibit adherence of mouse peritoneal M phi to serum-coated Falcon surfaces. Heparin inhibited M phi-adherence in serum containing medium and in higher concentrations stimulated the adherence inhibitory effect of PDS, especially in Ca-depleted medium. This effect of heparin may be due to its polyanionic character, as dextran sulphate but not dextran induced similar changes. The effect of heparin to increase the sensitivity of membrane SH-groups against SH-reactive agents was demonstrated also by cytotoxicity experiments. It is concluded that heparin makes the M phi-membrane unstable, by exposing some hidden SH-groups playing a role in membrane function.
Insights
Heparin affects macrophage adherence and membrane thiol reactivity. This suggests heparin destabilizes macrophage membranes by exposing thiol groups, impacting cell function.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophage (M phi) adherence is crucial for immune responses.
- Membrane thiol groups play a role in cell function and reactivity.
- Heparin is a known anticoagulant with potential immunomodulatory effects.
Purpose of the Study:
- To investigate the impact of heparin on macrophage adherence.
- To examine heparin's influence on the reactivity of macrophage membrane thiol groups.
- To elucidate the mechanism behind heparin's effects on macrophage membranes.
Main Methods:
- Studied macrophage adherence to serum-coated surfaces.
- Assessed the reactivity of membrane SH-groups using SH-oxidizing agents like 4,4'-dithiodipyridine (PDS).
- Conducted cytotoxicity experiments to evaluate heparin's effect on membrane thiol sensitivity.
Main Results:
- Various SH-reactive agents, excluding DTNB, inhibited macrophage adherence.
- Heparin inhibited macrophage adherence and, at higher concentrations, enhanced the adherence inhibitory effect of PDS, particularly in calcium-depleted conditions.
- Heparin increased the sensitivity of membrane SH-groups to SH-reactive agents, as shown by cytotoxicity assays.
Conclusions:
- Heparin's effects on macrophage adherence and membrane thiol reactivity are linked to its polyanionic nature.
- Heparin appears to destabilize the macrophage membrane by exposing previously hidden SH-groups.
- These exposed SH-groups likely play a significant role in macrophage membrane function and cellular responses.