HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print October 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0605321v1 78/6/1281    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shibata, Y. Articles by Myrvik, Q. N. Search for Related Content PubMed PubMed Citation Articles by Shibata, Y. Articles by Myrvik, Q. N.

(Journal of Leukocyte Biology. 2005;78:1281-1290.)
© 2005 by Society for Leukocyte Biology

Splenic PGE₂-releasing macrophages regulate Th1 and Th2 immune responses in mice treated with heat-killed BCG

Yoshimi Shibata^*,1, Ruth Ann Henriksen, Ikuro Honda, Reiko M. Nakamura and Quentin N. Myrvik

^* Department of Biomedical Sciences, Florida Atlantic University, Boca Raton;
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina;
Japan BCG Laboratory, Tokyo; and
404 Palmeto Drive, Caswell Beach, North Carolina

¹ Correspondence: Department of Biomedical Sciences, Florida Atlantic University, 777 Glades Rd., P.O. Box 3091, Boca Raton, FL 33431-0991. E-mail: yshibata{at}fau.edu

Hosts infected with low doses of mycobacteria develop T helper cell type 1 (Th1) immunity, but at relatively higher doses, a switch to Th2 immunity occurs. Prostaglandin E₂ (PGE₂) is a proposed mediator of the Th1-to-Th2 shift of immune responses, and mycobacterial products induce PGE₂-releasing macrophages (PGE₂-MØ) in the mouse spleen in a dose-dependent manner. Splenic PGE₂-M Ø from Balb/c mice, given 0.01 or 1 mg heat-killed (HK) Mycobacterium bovis bacillus Calmette-Guerin (BCG) intraperitoneally (i.p.), were characterized by the ex vivo release of PGE₂ (>10 ng/10⁶ cells), cytokine production, and expression of PGG/H synthase (PGHS)-1, PGHS-2, cytosolic PGE synthase (PGES), and microsomal PGES-1. At Day 14 after the treatment, mice treated with 1 mg, but not 0.01 mg, BCG had increased levels of PGHS-2⁺ PGE₂-MØ, total serum immunoglobulin E (IgE), and serum IgG1 antibodies (Th2 responses) against heat shock protein 65 and purified protein derivative. Cultures of spleen cells isolated from these mice expressed interleukin (IL)-4 and IL-10 in recall responses. Treatment of mice receiving 1 mg BCG with NS-398 (a PGHS-2 inhibitor, 10 mg/kg i.p., daily) resulted in enhanced interferon- (IFN-) production with reduced IL-4 and IL-10 production in recall responses. This treatment also resulted in decreased total serum IgE levels. Treatment of C57Bl/6 mice with HK-BCG (0.5 mg dose) also induced a mixture of Th1 and Th2 responses, although IFN- production was markedly increased, and IL-4 was decreased compared with Balb/c mice. Thus, our results indicate that by 14 days following treatment of mice with high doses of HK-BCG, splenic PGE₂-MØ formation is associated with a PGHS-2-dependent shift from Th1-to-Th2 immune responses.

Key Words: PGHS-2 (Cox-2) • cPGES • purified protein derivative • splenic macrophages • PGE₂ • Th1-to-Th2 shift

This article has been cited by other articles:

				F. Kojima, M. Kapoor, L. Yang, E. L. Fleishaker, M. R. Ward, S. U. Monrad, P. C. Kottangada, C. Q. Pace, J. A. Clark, J. G. Woodward, et al. Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice J. Immunol., June 15, 2008; 180(12): 8361 - 8368. [Abstract] [Full Text] [PDF]

				M. Yamashita, T. Shinohara, S. Tsuji, Q. N. Myrvik, A. Nishiyama, R. A. Henriksen, and Y. Shibata Catalytically Inactive Cyclooxygenase 2 and Absence of Prostaglandin E2 Biosynthesis in Murine Peritoneal Macrophages following In Vivo Phagocytosis of Heat-Killed Mycobacterium bovis Bacillus Calmette-Guerin J. Immunol., November 15, 2007; 179(10): 7072 - 7078. [Abstract] [Full Text] [PDF]

				J. R. Erb-Downward and M. C. Noverr Characterization of Prostaglandin E2 Production by Candida albicans Infect. Immun., July 1, 2007; 75(7): 3498 - 3505. [Abstract] [Full Text] [PDF]

				M. Yamashita, S. Tsuji, A. Nishiyama, Q. N. Myrvik, R. A. Henriksen, and Y. Shibata Differential subcellular localization of COX-2 in macrophages phagocytosing heat-killed Mycobacterium bovis BCG Am J Physiol Cell Physiol, July 1, 2007; 293(1): C184 - C190. [Abstract] [Full Text] [PDF]

				Y. Shibata, J. Gabbard, M. Yamashita, S. Tsuji, M. Smith, A. Nishiyama, R. A. Henriksen, and Q. N. Myrvik Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation--role of IL-10 and bone marrow precursors J. Leukoc. Biol., September 1, 2006; 80(3): 590 - 598. [Abstract] [Full Text] [PDF]