Target cells for interferon induction by BL-20803

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• The reticuloendothelial system plays a role in immune responses.
• Interferon induction is a critical aspect of antiviral defense.
• The compound 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazola-3,4-b-quinoline dihydrochloride (BL-20803) is a low-molecular-weight inducer.

Purpose of the Study:

• To investigate the role of specific reticuloendothelial cells in the interferon response to BL-20803.
• To identify the cellular targets responsible for interferon production induced by BL-20803.

Main Methods:

• In vitro culture of mouse spleen adherent cells with BL-20803.
• Isolation and testing of adherent cells from peritoneal washes.
• In vivo treatment of mice with antisera against specific cell types (adherent cells, thymocytes, nonadherent spleen cells).
• Assessment of interferon production following BL-20803 administration.
• Pretreatment of mice with zymosan to modulate responsiveness.

Main Results:

• Mouse spleen adherent cells cultured in vitro produced interferon upon exposure to BL-20803.
• Adherent cells from peritoneal washes were unresponsive to BL-20803.
• Antiserum to mouse adherent cells suppressed interferon production by at least 65%.
• Antisera to thymocytes or nonadherent spleen cells did not suppress interferon production.
• Zymosan pretreatment induced circulating interferon in normally unresponsive mice.
• No potentiation of interferon response was observed in actively immunized mice.

Conclusions:

• Fixed macrophages in mice are likely the primary cellular targets for interferon induction by BL-20803.
• Specific adherent cell populations are responsible for the interferon response to BL-20803.