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Down-regulation of Ia expression on macrophages by sea star factor
Abstract:
Sea star factor (SSF), a protein of 39,000 Da isolated from the coelomocytes of Asterias forbesi, was found to inhibit the induction of Ia expression on murine macrophages by concanavalin A supernatants. Addition of SSF to cultured macrophages at the same time as the lymphokine preparation significantly reduced the percentage Ia+ cells after 5 days culture, compared to cultures given lymphokine only. Intraperitoneal injection of SSF also reduced the percentage Ia+ peritoneal exudate macrophages by three-fourths in Listeria-infected mice. Addition of the cyclo-oxygenase inhibitor, indomethacin, to macrophage cultures reversed this Ia-suppressive effect of SSF. Since macrophages from endotoxin-unresponsive and endotoxin-responsive mice were both sensitive to the Ia-inhibitory effect of SSF, the induction of arachidonic acid metabolism and the inhibition of Ia appear to be independent of the action of endotoxin. The SSF-induced down regulation of Ia expression may be a major factor in the suppression of primary immune responses to T-dependent antigens previously noted in studies with SSF.
Insights
Sea star factor (SSF) inhibits Ia expression on macrophages, a key immune cell. This protein
Area of Science:
- Immunology
- Marine Biology
- Biochemistry
Background:
- Sea star factor (SSF) is a protein isolated from the marine invertebrate Asterias forbesi.
- Ia expression on macrophages is crucial for immune responses.
- Previous studies noted SSF suppresses primary immune responses to T-dependent antigens.
Purpose of the Study:
- To investigate the mechanism by which Sea star factor (SSF) affects Ia expression on murine macrophages.
- To determine if SSF's effect on Ia expression is linked to arachidonic acid metabolism and endotoxin activity.
Main Methods:
- Inhibition of Ia expression on cultured murine macrophages using SSF and concanavalin A supernatants.
- Assessment of Ia+ cells after 5 days of culture.
- Intraperitoneal injection of SSF in Listeria-infected mice to evaluate Ia+ peritoneal exudate macrophages.
- Addition of indomethacin, a cyclo-oxygenase inhibitor, to macrophage cultures to assess its effect on SSF-induced Ia suppression.
Main Results:
- SSF significantly reduced the percentage of Ia+ cells in cultured macrophages.
- Intraperitoneal SSF administration reduced Ia+ peritoneal exudate macrophages by 75% in infected mice.
- Indomethacin reversed the Ia-suppressive effect of SSF, suggesting involvement of cyclo-oxygenase pathway.
- SSF's inhibitory effect on Ia expression was observed in both endotoxin-unresponsive and responsive mice, indicating independence from endotoxin action.
Conclusions:
- Sea star factor (SSF) down-regulates Ia expression on macrophages.
- The mechanism involves the induction of arachidonic acid metabolism, independent of endotoxin.
- SSF-induced Ia suppression may explain its previously observed role in suppressing T-dependent immune responses.