Differential subcellular localization of COX-2 in macrophages phagocytosing heat-killed Mycobacterium bovis BCG.
Cyclooxygenase-2 (COX-2)-mediated prostaglandin E(2) (PGE(2)) biosynthesis by macrophages downregulates microbicidal activities in innate and acquired immune responses against intracellular bacteria. Previous studies in mice showed that intraperitoneal administration of heat-killed Mycobacterium bovis bacillus Calmette-Guérin (HK-BCG) resulted in induction of splenic PGE(2)-releasing macrophages in 7-14 days. In contrast, HK-BCG induced catalytically inactive COX-2 at relatively high levels in the macrophages within 1 day. In the present study, we found that COX-2 was localized subcellularly in the nuclear envelope (NE) 7 and 14 days after HK-BCG treatment, whereas COX-2 was dissociated from the NE 1 day after treatment. At 1 day after treatment, the majority of COX-2-positive macrophages had phagocytosed HK-BCG. In contrast, no intracellular HK-BCG was detected 7 and 14 days after treatment in COX-2-positive macrophages, where COX-2 was associated with the NE. However, when macrophages phagocytosed HK-BCG in vitro, all COX-2 was associated with the NE. Thus the administration of HK-BCG induces the biphasic COX-2 expression of an NE-dissociated catalytically inactive or an NE-associated catalytically active form in splenic macrophages. The catalytically inactive COX-2-positive macrophages develop microbicidal activities effectively, since they lack PGE(2) biosynthesis.
Yamashita
Makiko
M
Dept. of Biomedical Sciences, Florida Atlantic University, 777 Glades Rd., PO Box 3091, Boca Raton, FL 33431-0991, USA.
Tsuji
Shoutaro
S
Nishiyama
Akihito
A
Myrvik
Quentin N
QN
Henriksen
Ruth Ann
RA
Shibata
Yoshimi
Y
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003593:Cytoplasm / Q000201:enzymology / Q000276:immunology; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009685:Nuclear Envelope / Q000201:enzymology / Q000276:immunology; D010587:Phagocytosis; D021381:Protein Transport; D013154:Spleen / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
D001500:BCG Vaccine; D015164:Vaccines, Inactivated; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone