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 E2 (PGE2) 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 PGE2 following elicitation with calcium ionophore A23187. For further characterization of in vivo requirements for development of PGE2-releasing MØ (PGE2-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, PGE2 biosynthesis by these MØ was not increased. Thus, expression of COX-2 is not sufficient to induce PGE2 production in vivo or in vitro. In sharp contrast, 14 days after HK-BCG treatment, PGE2 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 PGE2-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 PGE2 production.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 05, 2006
- Source ID
- 10.1189/jlb.1205737
Entities
People
- Akihito Nishiyama
- Jon Gabbard
- Makiko Yamashita
- Mike Smith
- Quentin N. Myrvik
- Ruth Ann Henriksen
- Shoutaro Tsuji
- Yoshimi Shibata
Organizations
- East Carolina University
- Florida Atlantic University
- National Institutes of Health
- United States Department of Defense