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Shibata, Y. et al.

Shibata, Gabbard, Yamashita, Tsuji, Smith, Nishiyama, Henriksen, Myrvik,

Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation--role of IL-10 and bone marrow precursors.

Previous studies have shown that prostaglandin E(2) (PGE(2)) release by splenic F4/80(+) cyclooxygenase (COX)-2(+) macrophages (MÃ˜) isolated from mice, treated with mycobacterial components, plays a major role in the regulation of immune responses. However, splenic MÃ˜, 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 MÃ˜ (PGE(2)-MÃ˜), 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 MÃ˜ of both mouse strains. However, PGE(2) biosynthesis by these MÃ˜ 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 MÃ˜ 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)-MÃ˜ 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(+) MÃ˜ may be responsible for the increased PGE(2) production.[1]

References

Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation--role of IL-10 and bone marrow precursors. Shibata, Y., Gabbard, J., Yamashita, M., Tsuji, S., Smith, M., Nishiyama, A., Henriksen, R.A., Myrvik, Q.N. J. Leukoc. Biol. (2006) [Pubmed]

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