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

J. Biol. Chem., Vol. 281, Issue 10, 6691-6698, March 10, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/10/6691    most recent M508314200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Balestrieri, B. Articles by Arm, J. P. Search for Related Content PubMed PubMed Citation Articles by Balestrieri, B. Articles by Arm, J. P. Social Bookmarking                      What's this?

Group V Secretory Phospholipase A₂ Translocates to the Phagosome after Zymosan Stimulation of Mouse Peritoneal Macrophages and Regulates Phagocytosis^*

Barbara Balestrieri, Victor W. Hsu, Huiya Gilbert, Christina C. Leslie^¶, Won K. Han^||, Joseph V. Bonventre^||, and Jonathan P. Arm^**1

From the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, the ^¶Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, the Division of Rheumatology, Immunology, and Allergy, the ^|| Renal Division, and the ^**Partners Asthma Center, Brigham and Women's Hospital, Boston, Massachusetts 02115

We have previously reported that group V secretory phospholipase A₂ (sPLA₂) amplifies the action of cytosolic phospholipase A₂(cPLA₂) in regulating eicosanoid biosynthesis by mouse peritoneal macrophages stimulated with zymosan (Satake, Y., Diaz, B. L., Balestrieri, B., Lam, B. K., Kanaoka, Y., Grusby, M. J., and Arm, J. P. (2004) J. Biol. Chem. 279, 16488-16494). To further understand the role of group V sPLA₂, we studied its localization in resting mouse peritoneal macrophages before and after stimulation with zymosan and the effect of deletion of the gene encoding group V sPLA₂ on phagocytosis of zymosan. We report that group V sPLA₂ is present in the Golgi apparatus and recycling endosome in the juxtanuclear region of resting peritoneal macrophages. Upon ingestion of zymosan by mouse peritoneal macrophages, group V sPLA₂ is recruited to the phagosome. There it co-localizes with cPLA ₂ , 5-lipoxygenase, 5-lipoxygenase-activating protein, and leukotriene C₄ synthase. Using immunostaining for the cysteinyl leukotrienes in carbodiimide-fixed cells, we show, for the first time, that the phagosome is a site of cysteinyl leukotriene formation. Furthermore, peritoneal macrophages from group V sPLA₂-null mice demonstrated a >50% attenuation in phagocytosis of zymosan particles, which was restored by adenoviral expression of group V sPLA₂ but IIA not group sPLA₂. These data demonstrate that group V sPLA₂ contributes to the innate immune response both through regulation of eicosanoid generation in response to a phagocytic stimulus and also as a component of the phagocytic machinery.

Received for publication, July 29, 2005 , and in revised form, December 8, 2005.

^* This work was supported by National Institutes of Health Grants HL36110, HL070946, HL34303, HL61378, DK38452, DK39773, DK74099 and AI07306 and the Centro Nazionale delle Richerche Fellowship program. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Brigham and Women's Hospital, Smith Research Bldg., Rm. 638B, 1, Jimmy Fund Way, Boston, MA 02115. Tel.: 617-525-1305; Fax: 617-525-1310; E-mail: jarm{at}rics.bwh.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Valera, N. Fernandez, A. G. Trinidad, S. Alonso, G. D. Brown, A. Alonso, and M. S. Crespo Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells J. Immunol., April 15, 2008; 180(8): 5727 - 5736. [Abstract] [Full Text] [PDF]

				E. J. Swindle, J. W. Coleman, F. R. DeLeo, and D. D. Metcalfe Fc{epsilon}RI- and Fc{gamma} Receptor-Mediated Production of Reactive Oxygen Species by Mast Cells Is Lipoxygenase- and Cyclooxygenase-Dependent and NADPH Oxidase-Independent J. Immunol., November 15, 2007; 179(10): 7059 - 7071. [Abstract] [Full Text] [PDF]

				N. M. Munoz, A. Y. Meliton, J. P. Arm, J. V. Bonventre, W. Cho, and A. R. Leff Deletion of Secretory Group V Phospholipase A2 Attenuates Cell Migration and Airway Hyperresponsiveness in Immunosensitized Mice J. Immunol., October 1, 2007; 179(7): 4800 - 4807. [Abstract] [Full Text] [PDF]

				E. Kikawada, J. V. Bonventre, and J. P. Arm Group V secretory PLA2 regulates TLR2-dependent eicosanoid generation in mouse mast cells through amplification of ERK and cPLA2{alpha} activation Blood, July 15, 2007; 110(2): 561 - 567. [Abstract] [Full Text] [PDF]

				M. Kolko, J. Wang, C. Zhan, K. A. Poulsen, J. U. Prause, M. H. Nissen, S. Heegaard, and N. G. Bazan Identification of Intracellular Phospholipases A2 in the Human Eye: Involvement in Phagocytosis of Photoreceptor Outer Segments Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1401 - 1409. [Abstract] [Full Text] [PDF]

				T. Ueyama, T. Tatsuno, T. Kawasaki, S. Tsujibe, Y. Shirai, H. Sumimoto, T. L. Leto, and N. Saito A Regulated Adaptor Function of p40phox: Distinct p67phox Membrane Targeting by p40phox and by p47phox Mol. Biol. Cell, February 1, 2007; 18(2): 441 - 454. [Abstract] [Full Text] [PDF]

				M. Ohtsuki, Y. Taketomi, S. Arata, S. Masuda, Y. Ishikawa, T. Ishii, Y. Takanezawa, J. Aoki, H. Arai, K. Yamamoto, et al. Transgenic Expression of Group V, but Not Group X, Secreted Phospholipase A2 in Mice Leads to Neonatal Lethality because of Lung Dysfunction J. Biol. Chem., November 24, 2006; 281(47): 36420 - 36433. [Abstract] [Full Text] [PDF]