title: Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation--role of IL-10 and bone marrow precursors.
abstract: Previous studies have shown that prostaglandin E(2) (PGE(2)) release by splenic F4/80(+) cyclooxygenase (COX)-2(+) macrophages (MØ) isolated from mice, treated with mycobacterial components, plays a major role in the regulation of immune responses. However, splenic MØ, isolated from untreated mice and treated in vitro with lipopolysaccharide and interferon-gamma, express COX-1 and COX-2 within 1 day but release only minimal amounts of PGE(2) following elicitation with calcium ionophore A23187. For further characterization of in vivo requirements for development of PGE(2)-releasing MØ (PGE(2)-MØ), C57Bl/6 [wild-type (WT)], and interleukin (IL)-10-deficient (IL-10(-/-)) mice were treated intraperitoneally with heat-killed Mycobacterium bovis bacillus Calmette-Guerin (HK-BCG). One day following injection, COX-2 was induced in splenic MØ of both mouse strains. However, PGE(2) biosynthesis by these MØ was not increased. Thus, expression of COX-2 is not sufficient to induce PGE(2) production in vivo or in vitro. In sharp contrast, 14 days after HK-BCG treatment, PGE(2) release by COX-2(+) splenic MØ increased as much as sevenfold, and a greater increase was seen in IL-10(-/-) cells than in WT cells. To further determine whether the 14-day splenic PGE(2)-MØ could be derived from bone marrow precursors, we established a chimera in which bone marrow cells were transfused from green fluorescent protein (GFP)-transgenic donors to WT mice. Donors and recipients were treated with HK-BCG simultaneously, and marrow transfusion was performed on Days 1 and 2. On Day 14 after BCG treatment, a significant number of spleen cells coexpressed COX-2 and GFP, indicating that bone marrow-derived COX-2(+) MØ may be responsible for the increased PGE(2) production.
authors.affiliation: Department of Biomedical Sciences, Florida Atlantic University, 777 Glades Rd., P.O. Box 3091, Boca Raton, 33431-0991, USA. yshibata@fau.edu
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shibata
authors.forename: Jon
authors.initials: J
authors.lastname: Gabbard
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamashita
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Tsuji
authors.forename: Mike
authors.initials: M
authors.lastname: Smith
authors.forename: Akihito
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Henriksen
authors.forename: Quentin N
authors.initials: QN
authors.lastname: Myrvik
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002474:Cell-Free System / Q000378:metabolism; D002678:Chimera; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D001500:BCG Vaccine; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D015232:Dinoprostone