Skip to main content
SpringerLink
Log in

Leukotriene-B4 Receptor and Signal Transduction

  • Conference paper
Advances in Eicosanoid Research

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 31))

Abstract

When cells are stimulated with various agonists, cells release arachidonic acid by the action of phospholipases, and arachidonic acid is further converted to various types of leukotrienes (LTs; Samuelsson et al. 1987; Shimizu and Wolfe 1990; Serhan et al. 1996). Recent fiindings from our laboratories and others have shown that cytosolic phospholipase A2 (cPLA2) plays a dominant role in arachidonate release in various cells (Bonventre et al. 1997; Leslie 1997; Uozumi et al. 1997). We isolated arachidonate 5-lipoxygenase from potato tubers for the first time and found that a single enzyme catalyzes both lipoxygenation and dehydration to yield LTA4 (Shimizu et al. 1984).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akbar GKM, Dasari VR, Webb TE, Ayyanathan K, Pillarisetti K, Sandhu AK, Athwal RS, Daniel JL, Ashby B, Barnard EA, Kunapuli SP (1996) Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells. J Biol Chem 271:1 8363–18367

    Google Scholar 

  • Alkhaatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA (1996) CC CKR5: a RANTES, MIP-1 α, MIP-1 ß receptor as a fusion cofactor for macrophage-tropic HIV- 1. Science 272:1955–1958

    Article  Google Scholar 

  • Anonymous (1998) 1998 Receptor and ion channel nomenclature. Trends Pharmacol Sci 1998 [suppl]:1–98

    Google Scholar 

  • Bjork J, Hedqvist P, Arfors KE (1982) Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes. Inflammation 6:189–200

    Article  CAS  Google Scholar 

  • Bonventre JV, Huang Z, Taheri MR, O’Leary E, Li E, Moskowitz MA, Sapirstein A (1997) Reduced fertility and post-ischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature 390:622–625

    Article  CAS  Google Scholar 

  • Brooks CD, Summer JB (1996) Modulators of leukotriene biosynthesis and receptor activation. J Med Chem 39:2629–2654

    Article  CAS  Google Scholar 

  • Chen X-S, Sheller R, Johnson N, Func C (1993) Role of leukotriene revealed by targeted disruption of the 5-lipoxygenase gene. Nature 372:179–182

    Article  Google Scholar 

  • Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J (1996) The ßchemokine receptors CCR3 and CCR5 facilitate infection by primary HIV- 1 isolates. Cell 85:1135–1148

    Article  CAS  Google Scholar 

  • Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV 1. Nature 381:661–666

    Article  CAS  Google Scholar 

  • Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W (1996) The PPARα—leukotriene B4 pathway to inflammation control. Nature 384:39–43

    Article  CAS  Google Scholar 

  • Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA (1988) Cloning of the cDNA for human 5-lipoxygenase. Proc Natl Acad Sci U S A 85:416–420

    Article  CAS  Google Scholar 

  • Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW (1996) A dual-tropic primary HIV- 1 isolate that uses fusin and the ß-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85:1149–1158

    Article  CAS  Google Scholar 

  • Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA (1996) HIV- 1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667–673

    Article  CAS  Google Scholar 

  • Endres MJ, Clapham PR, Marsh M, Ahuja M, Turner JD, McKnight A, Thomas JF, Stoebenau-Haggarty B, Choe S, Vance PJ, Wells TN, Power CA, Sutterwala SS, Doms RW, Landau NR, Hoxie JA (1996) CD4-independent infection by HIV- 2 is mediated by fusin/CXCR4. Cell 87:745–756

    Article  CAS  Google Scholar 

  • Ensor CM, Zhang H, Tai HH (1998) Purifiication, cDNA cloning and expression of 15-oxoprostaglandin 13-reductase from pig lung. Biochem J 330:103–108

    CAS  Google Scholar 

  • Feng Y, Broder CC, Kennedy PE, Berger EA(1996) HIV- 1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G-protein-coupled receptor. Science 272:872–877

    CAS  Google Scholar 

  • Ford-Hutchinson A, Doig MV, Shipley ME, Smith MJ (1980) Leukotriene B4, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265

    Article  CAS  Google Scholar 

  • Gaudreau R, Le Gouill C, Metaoui S, Lemire S, Stankova J, Rola-Pleszczynski M (1998) Signalling through the leukotriene B4 receptor involves both αi and αl6, but not aq or al 1 G-protein subunits. Biochem J 335:15–18

    CAS  Google Scholar 

  • Griffiiths RJ, Pettipher ER, Koch K, Farrell CA, Breslow R, Conklyn MJ, Smith MA, Hackman BC, Wimberly DJ, Milici AJ, McNeish JD (1995) Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Proc Natl Acad Sci U S A 92:517–521

    Article  Google Scholar 

  • Griffiiths RJ, Smith MA, Roach ML, Stock JL, Stam EJ, Milici AJ, Scampoli DN, Eskra JD, Byrum RS, Koller BH, McNeish JD (1997) Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-defiicient mice. J Exp Med 185:1123–1129

    Article  Google Scholar 

  • Hirabayashi T, Kume K, Hirose K, Yokomizo T, Iino M, Itoh H, Shimizu T (1999) Critical duration of intracellular Ca2+ response required for continuous translocation and activation of cytosolic phospholipase A2. J Biol Chem 274:5163–5169

    Article  CAS  Google Scholar 

  • Hoshino M, Izumi T, Shimizu T (1998) Leukotriene D4 activates mitogen-activated protein kinase through a protein kinase Cα-Raf-l-dependent pathway in human monocytic leukemia THP-1 cells. J Biol Chem 273:4878–4882

    Article  CAS  Google Scholar 

  • Huang WW, Garcia-Zepeda EA, Sauty A, Oettgen HC, Rothenberg ME, Luster AD (1998) Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils. J Exp Med 188:1063–1074

    Article  CAS  Google Scholar 

  • Igarashi T, Yokornizo T, Tsutsumi O, Taketani Y, Shimizu T, Izumi T (1999) Characterization of the leukotriene B4 receptor in porcine leukocytes. Separation and reconstitution with heterotrimeric GTP-binding proteins. Eur J Biochem 259:419–425

    Article  CAS  Google Scholar 

  • Iversen L, Kragballe K, Ziboh VA (1997) Significance of leukotriene-A4 hydrolase in the pathogenesis of psoriasis. Skin Pharmacol 10:169–177

    Article  CAS  Google Scholar 

  • Kasimir S, Schönfeld W, Hilger RA, König W (1991) Analysis of leukotriene B4 metabolism in human promyelocytic HL-60 cells. Biochem J 279:283–288

    CAS  Google Scholar 

  • Khakh BS, Kennedy C (1998) Adenosine and ATP: progress in their receptor’s structures and functions. Trends Pharmacol Sci 19:39–41

    Article  CAS  Google Scholar 

  • Kikuta Y, Kusunose E, Endo K, Yamamoto S, Sogawa K, Fujii KY, Kusunose M (1993) A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expressioh of leukotriene B4 αhydroxylase. J Biol Chem 268:9376–9380

    CAS  Google Scholar 

  • Kumlin M, Dahlén S-E (1990) Characterization of formation and further metabolism of leukotrienes in the chopped human lung. Biochim Biophys Acta 1044:201–210

    Article  CAS  Google Scholar 

  • Lam BK, Penrose JF, Freeman GJ, Austen KF (1994) Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A 91:7663–7667

    Article  CAS  Google Scholar 

  • Leslie CC (1997) Properties and regulation of cytosolic phospholipase A2. J Biol Chem 272:16709–16712

    Article  CAS  Google Scholar 

  • Masuda H, Yokomizo T, Izumi T, Shimizu T(1999) cDNA cloning and characterization of guinea-pig leukotriene B4 receptor. Biochem J 342:79–85

    Article  CAS  Google Scholar 

  • Miki I, Watanabe T, Nakamura M, Seyama Y, Ui M, Sato F, Shimizu T (1990) Solubilization and characterization of leukotriene B4 receptor-GTP binding protein complex from porcine spleen. Biochem Biophys Res Commun 166 342–348

    Article  CAS  Google Scholar 

  • Minami M, Ohno S, Kawasaki H, Radmark O, Samuellson B, Jornvall H, Shimizu T, Seyama Y, Suzuki K (1987) Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. J Biol Chem 262:13873–13876

    CAS  Google Scholar 

  • Noiri E, Dickman K, Miller F, Romanov G, Romanov VI, Shaw R, Chambers AF, Rittling SR, Denhardt DT, Goligorsky MS (1999) Reduced tolerance to acute renal ischemia in mice with a targeted disruption of the osteopontin gene. Kidney Int 56:74–82

    Article  CAS  Google Scholar 

  • Oberle GP, Niemeyer J, Thaiss F, Schoeppe W, Stahl RA (1992) Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury. Kidney Int 42:69–74

    Article  CAS  Google Scholar 

  • Ohishi N, Minami M, Kobayashi J, Seyama Y, Hata J, Yotsumoto H, Takaku F, Shimizu T (1990) Immunological quantitation and immunohistochemical localization of leukotriene A4 hydrolase in guinea pig tissues. J Biol Chem 265:7520–7525

    CAS  Google Scholar 

  • Owman C, Nilsson C, Lolait S J (1996) Cloning of cDNA encoding a putative chemoattractant receptor. Genomics 37:187–194

    Article  CAS  Google Scholar 

  • Owman C, Sabirsh A, Boketoft A, Olde B (1997) Leukotriene B4 is the functional ligand binding to and activating the cloned chemoattractant receptor, CMKRL1. Biochem Biophys Res Commun 240:162–166

    Article  CAS  Google Scholar 

  • Owman C, Garzino-Demo A, Cocchi F, Popovic M, Sabirsh A, Gallo RC (1998) The leukotriene B4 receptor functions as a novel type of co-receptor mediating entry of primary HIV- 1 isolates into CD4-positive cells. Proc Natl Acad Sci U S A 95:9530–9534

    Article  CAS  Google Scholar 

  • Radmark O, Shimizu T, Jornvall H, Samuelsson B (1984) Leukotriene A4 hydrolase in human leukocytes. Purification and properties. J Biol Chem 259:12339–12345

    CAS  Google Scholar 

  • Rahman MA, Nakazawa M, Emancipator SN, Dunn MJ (1988) Increased leukotriene B4 synthesis in immune injured rat glomeruli. J Clin Invest 81:1945–1952

    Article  CAS  Google Scholar 

  • Reyes AA, Lefkowith J, Pippin J, Klahr S (1992) Role of the 5-lipooxygenase pathway in obstructive nephropathy. Kidney Int 41:100–106

    Article  CAS  Google Scholar 

  • Rouzer CA, Shimizu T, Sarnuelsson B (1985) On the nature of the 5-lipoxygenase reaction in human leukocytes: characterization of a membrane-associated stimulatory factor. Proc Natl Acad Sci U S A 82:7505–7509

    Article  CAS  Google Scholar 

  • Rouzer CA, Matsumoto T, Samuelsson B (1986) Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthase activities. Proc Natl Acad Sci U S A 83:857–861

    Article  CAS  Google Scholar 

  • Samuelsson B, Dahlén SE, Lindgren JÃ…, Rouzer CA, Serhan CN (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176

    Article  CAS  Google Scholar 

  • Serhan CN, Haeggstrom JZ, Leslie CC (1996) Lipid mediator networks in cell signaling: update and impact of cytokines. FASEB J 10:1147–1158

    CAS  Google Scholar 

  • Shimizu T, Wolfe LS (1990) Arachidonic acid cascade and signal transduction. J Neurochem 55:1–15

    Article  CAS  Google Scholar 

  • Shimizu T, Radmark O, Jornvall H, Samuelsson B (1984) Enzyme with dual activities catalyzes formation of leukotriene A4 from arachidonic acid. Proc Natl Acad Sci U S A 81:689–693

    Article  CAS  Google Scholar 

  • Shimizu T, Izumi T, Seyama Y, Tadokoro K, Radmark O, Samuelsson B (1986) Characterization of leukotriene A4 synthase from murine mast cells: evidence for its identity to arachidonate 5-lipoxygenase. Proc Natl Acad Sci U S A 83:4175–4179

    Article  CAS  Google Scholar 

  • Soberman RJ, Harper TW, Murphy RC, Austen KF (1985) Identifiication and functional characterization of leukotriene B4 20-hydroxylase of human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A 82:2292–2295

    Article  CAS  Google Scholar 

  • Turner CR, Breslow R, Conklyn MJ, Andresen CJ, Patterson DK, Lopez AA, Owens B, Lee P, Watson JW, Showell HJ (1996) In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma. J Clin Invest 97:381–387

    Article  CAS  Google Scholar 

  • Ueda N, Kaneko S, Yoshimoto T, Yamamoto S (1986) Purification of arachidonate 5-lipoxygenase from porcine leukocytes and its reactivity with hydroperoxyeicosatetraenoic acids. J Biol Chem 261:7982–7988

    CAS  Google Scholar 

  • Uozumi N, Kume K, Nagase T, Nakatani N, Ishii S, Tashiro F, Komagata Y, Maki K, Ikuta K, Ouchi Y, Miyazaki J-I, Shimizu T (1997) Role of cytosolic phospholipase A2 in allergic response and parturition. Nature 390:618–622

    Article  CAS  Google Scholar 

  • Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG Isakson PC (1994) Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A 91:9745–9749

    Article  CAS  Google Scholar 

  • Yokomizo T, Izumi T, Takahashi T, Kasama T, Kobayashi Y, Sato F, Taketani Y, Shimizu T (1993) Enzymatic inactivation of leukotriene B by a novel enzyme found in the porcine kidney. Purifiication and properties of leukotriene B 12-hydroxydehydrogenase. J Biol Chem 268:18128–18135

    CAS  Google Scholar 

  • Yokomizo T, Ogawa Y, Uozumi N, Kume K, Izumi T, Shimizu T (1996) cDNA cloning, expression, and mutagenesis study of leukotriene B4 12-hydroxydehydrogenase. J Biol Chem 271:2844–2850

    Article  CAS  Google Scholar 

  • Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T (1997) A G-proteincoupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387: 620–624

    Article  CAS  Google Scholar 

Download references

Authors
  1. T. Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Yokomizo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Izumi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    C. N. Serhan

  2. Dept. of Immunology, Berlex Biosciences, Richmond, CA, 94804-0099, USA

    H. D. Perez

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Shimizu, T., Yokomizo, T., Izumi, T. (2000). Leukotriene-B4 Receptor and Signal Transduction. In: Serhan, C.N., Perez, H.D. (eds) Advances in Eicosanoid Research. Ernst Schering Research Foundation Workshop, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04047-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04047-8_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04049-2

  • Online ISBN: 978-3-662-04047-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation