Proceedings of Annual Meeting of the Physiological Society of Japan
Proceedings of Annual Meeting of the Physiological Society of Japan
Session ID : 2LA-3
Conference information
Clearance of Apoptotic Cells and Erythroid Nuclei
*Shigekazu Nagata
Author information
Keywords: test, test, test
CONFERENCE PROCEEDINGS FREE ACCESS

Details
Abstract

Apoptosis is mediated by a cascade of caspases, which eventually activates a specific DNase (CAD). CAD−/− cells do not undergo DNA fragmentation during apoptosis, but their DNA is degraded by DNase II in macrophages after they are engulfed. DNase II−/− mice are embryonic lethal due to IFNΒ produced by macrophages carrying undigested DNA, indicating that mammalian DNA can activate innate immunity. Bacterial DNA activates innate immunity via a TLR-dependent system, but mammalian DNA does not use TLR to activate IFNΒ gene. When DNase II gene is inducibly inactivated after birth, they develop polyarthritis in an age-dependent manner. The mice carry numerous activated macrophages containing undigested DNA and produce TNFΑ. Administration of anti-TNFΑ blocks the development of polyarthritis, suggesting that TNFΑ produced by the macrophages is responsible to trigger the arthritis. Using the knowledge that DNA of apoptotic cells can be digested by macrophages, we established an assay for engulfment, and identified MFG-E8 that passes apoptotic cells to phagocytes. MFG-E8−/− macrophages in germinal center show a defect in engulfment. MFG-E8−/− mice produce antinuclear antibodies and suffer glomerulanephritis, confirming that if apoptotic cells are not efficiently engulfed, it will cause autoimmune diseases. Apoptotic cells expose phosphatidylserine (PS) on their surface in a caspase-dependent manner, and it is recognized by macrophages as an “eat me” signal. During erythropoiesis, nuclei are protruded from erythroid precursors, and engulfed by macrophages. We recently showed that nuclei protruded from erythroid precursors also expose PS on their surface. [J Physiol Sci. 2007;57 Suppl:S2]

Content from these authors
© 2007 The Physiological Society of Japan
Previous article Next article
feedback
Top