Premium
Heat‐killed BCG induces biphasic cyclooxygenase 2 + splenic macrophage formation—role of IL‐10 and bone marrow precursors
Author(s) -
Shibata Yoshimi,
Gabbard Jon,
Yamashita Makiko,
Tsuji Shoutaro,
Smith Mike,
Nishiyama Akihito,
Henriksen Ruth Ann,
Myrvik Quentin N.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1205737
Subject(s) - bone marrow , biology , macrophage , immunology , spleen , biochemistry , in vitro
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‐γ, 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.