Catalytically inactive cyclooxygenase 2 and absence of prostaglandin E2 biosynthesis in murine peritoneal macrophages following in vivo phagocytosis of heat-killed Mycobacterium bovis bacillus Calmette-Guérin.

Abstract

Over 25 years ago, it was observed that peritoneal macrophages (Mphi) isolated from mice given heat-killed Mycobacterium bovis bacillus Calmette-Guérin (HK-BCG) i.p. did not release PGE(2). However, when peritoneal Mphi from untreated mice are treated with HK-BCG in vitro, cyclooxygenase 2 (COX-2), a rate-limiting enzyme for PGE(2) biosynthesis, is expressed and the release of PGE(2) is increased. The present study of peritoneal Mphi obtained from C57BL/6 mice and treated either in vitro or in vivo with HK-BCG was undertaken to further characterize the cellular responses that result in suppression of PGE(2) release. The results indicate that Mphi treated with HK-BCG in vivo express constitutive COX-1 and inducible COX-2 that are catalytically inactive, are localized subcellularly in the cytoplasm, and are not associated with the nuclear envelope (NE). In contrast, Mphi treated in vitro express catalytically active COX-1 and COX-2 that are localized in the NE and diffusely in the cytoplasm. Thus, for local Mphi activated in vivo by HK-BCG, the results indicate that COX-1 and COX-2 dissociated from the NE are catalytically inactive, which accounts for the lack of PGE(2) production by local Mphi activated in vivo with HK-BCG. Our studies further indicate that the formation of catalytically inactive COX-2 is associated with in vivo phagocytosis of HK-BCG, and is not dependent on extracellular mediators produced by in vivo HK-BCG treatment. This attenuation of PGE(2) production may enhance Mphi-mediated innate and Th1-acquired immune responses against intracellular infections which are suppressed by PGE(2).

• Authors: Makiko Yamashita, Tsutomu Shinohara, Shoutaro Tsuji, Quentin N Myrvik, Akihito Nishiyama, Ruth Ann Henriksen, Yoshimi Shibata
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 179 Issue 10 Pg. 7072-8 (Nov 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17982098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Membrane Proteins
• Ptgs2 protein, mouse
• Cyclooxygenase 1
• Cyclooxygenase 2
• Ptgs1 protein, mouse
• Dinoprostone

Topics

• Animals
• Cells, Cultured
• Cyclooxygenase 1 (immunology, metabolism)
• Cyclooxygenase 2 (immunology, metabolism)
• Cytoplasm (enzymology, immunology)
• Dinoprostone (biosynthesis, immunology)
• Female
• Immunity, Innate
• Macrophages, Peritoneal (enzymology, immunology)
• Membrane Proteins (immunology, metabolism)
• Mice
• Mycobacterium bovis (immunology)
• Nuclear Envelope (enzymology, immunology)
• Phagocytosis (immunology)
• Th1 Cells (enzymology, immunology)