Importance of Group X-secreted Phospholipase A2 in Allergen-induced Airway Inflammation and Remodeling in a Mouse Asthma Model

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Apr 4

PMID 17403936

Citations 93

Authors

William R Henderson Jr

Emil Y Chi

James G Bollinger

Ying-Tzang Tien

Xin Ye

Luca Castelli

Yuri P Rubtsov

Alan G Singer

Gertrude K S Chiang

Timo Nevalainen

Alexander Y Rudensky

Michael H Gelb

Affiliations

Soon will be listed here.

Abstract

Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A(2)s (PLA(2)s), most notably cytosolic PLA(2)-alpha. 10 secreted PLA(2)s (sPLA(2)s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA(2) (sPLA(2)-X), the sPLA(2) with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA(2)-X(-/-) mice, compared with those of sPLA(2)-X(+/+) littermates, had significant reduction in ovalbumin-induced infiltration by CD4(+) and CD8(+) T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA(2)-X as a novel therapeutic target for asthma.

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References

Hanasaki K, Ono T, SAIGA A, Morioka Y, Ikeda M, Kawamoto K . Purified group X secretory phospholipase A(2) induced prominent release of arachidonic acid from human myeloid leukemia cells. J Biol Chem. 1999; 274(48):34203-11. DOI: 10.1074/jbc.274.48.34203. View

Miyahara N, Swanson B, Takeda K, Taube C, Miyahara S, Kodama T . Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med. 2004; 10(8):865-9. DOI: 10.1038/nm1081. View

Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K . Prostaglandin D2 as a mediator of allergic asthma. Science. 2000; 287(5460):2013-7. DOI: 10.1126/science.287.5460.2013. View

Seeds M, Jones K, Hite R, Willingham M, Borgerink H, Woodruff R . Cell-specific expression of group X and group V secretory phospholipases A(2) in human lung airway epithelial cells. Am J Respir Cell Mol Biol. 2000; 23(1):37-44. DOI: 10.1165/ajrcmb.23.1.4034. View

Gijon M, Spencer D, Siddiqi A, Bonventre J, Leslie C . Cytosolic phospholipase A2 is required for macrophage arachidonic acid release by agonists that Do and Do not mobilize calcium. Novel role of mitogen-activated protein kinase pathways in cytosolic phospholipase A2 regulation. J Biol Chem. 2000; 275(26):20146-56. DOI: 10.1074/jbc.M908941199. View

Valentin E, Lambeau G . Increasing molecular diversity of secreted phospholipases A(2) and their receptors and binding proteins. Biochim Biophys Acta. 2000; 1488(1-2):59-70. DOI: 10.1016/s1388-1981(00)00110-4. View

Kay A . Allergy and allergic diseases. First of two parts. N Engl J Med. 2001; 344(1):30-7. DOI: 10.1056/NEJM200101043440106. View

SAIGA A, Morioka Y, Ono T, Nakano K, Ishimoto Y, Arita H . Group X secretory phospholipase A(2) induces potent productions of various lipid mediators in mouse peritoneal macrophages. Biochim Biophys Acta. 2001; 1530(1):67-76. DOI: 10.1016/s1388-1981(00)00167-0. View

Akiba S, Hatazawa R, Ono K, Kitatani K, Hayama M, Sato T . Secretory phospholipase A2 mediates cooperative prostaglandin generation by growth factor and cytokine independently of preceding cytosolic phospholipase A2 expression in rat gastric epithelial cells. J Biol Chem. 2001; 276(24):21854-62. DOI: 10.1074/jbc.M010201200. View

10.

Ghomashchi F, Stewart A, Hefner Y, Ramanadham S, Turk J, Leslie C . A pyrrolidine-based specific inhibitor of cytosolic phospholipase A(2)alpha blocks arachidonic acid release in a variety of mammalian cells. Biochim Biophys Acta. 2001; 1513(2):160-6. DOI: 10.1016/s0005-2736(01)00349-2. View

11.

Lee C, Homer R, Zhu Z, Lanone S, Wang X, Koteliansky V . Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001; 194(6):809-21. PMC: 2195954. DOI: 10.1084/jem.194.6.809. View

12.

Henderson Jr W, Tang L, Chu S, Tsao S, Chiang G, Jones F . A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model. Am J Respir Crit Care Med. 2002; 165(1):108-16. DOI: 10.1164/ajrccm.165.1.2105051. View

13.

Kirkham S, Sheehan J, Knight D, Richardson P, Thornton D . Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J. 2002; 361(Pt 3):537-46. PMC: 1222336. DOI: 10.1042/0264-6021:3610537. View

14.

Degousee N, Ghomashchi F, Stefanski E, Singer A, Smart B, Borregaard N . Groups IV, V, and X phospholipases A2s in human neutrophils: role in eicosanoid production and gram-negative bacterial phospholipid hydrolysis. J Biol Chem. 2001; 277(7):5061-73. DOI: 10.1074/jbc.M109083200. View

15.

Asakura T, Ishii Y, Chibana K, Fukuda T . Leukotriene D4 stimulates collagen production from myofibroblasts transformed by TGF-beta. J Allergy Clin Immunol. 2004; 114(2):310-5. DOI: 10.1016/j.jaci.2004.04.037. View

16.

Hamberg M, Samuelsson B . On the metabolism of prostaglandins E 1 and E 2 in man. J Biol Chem. 1971; 246(22):6713-21. View

17.

Fitzpatrick F, Wynalda M . Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro. J Biol Chem. 1983; 258(19):11713-8. View

18.

Pruzanski W, Vadas P, Stefanski E, Urowitz M . Phospholipase A2 activity in sera and synovial fluids in rheumatoid arthritis and osteoarthritis. Its possible role as a proinflammatory enzyme. J Rheumatol. 1985; 12(2):211-6. View

19.

Neill M, Henderson W, Klebanoff S . Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages. J Exp Med. 1985; 162(5):1634-44. PMC: 2187916. DOI: 10.1084/jem.162.5.1634. View

20.

Peters-Golden M, Feyssa A . Transcellular eicosanoid synthesis in cocultures of alveolar epithelial cells and macrophages. Am J Physiol. 1993; 264(5 Pt 1):L438-47. DOI: 10.1152/ajplung.1993.264.5.L438. View