Abstract
The 5-lipoxygenase pathway for oxidative metabolism of unsaturated fatty acids was first recognized less than 10 years ago with the definition of 5S-hydroxy-eicosatetraenoic acid (5-HETE) as a product, l and its potential biological relevance to inflammation was defined solely by the modest chemotactic activity of 5-HETE.2 However, major interest in this pathway did not occur until 5 years ago when leukotriene B4 (LTB4), 5S,12R-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid was first described3 and the elusive “slow reacting substance of anaphylaxis (SRS-A),” was chemically defined as three additional leukotriene products of this pathway: LTC4, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic acido; LTD4, 5S-hydroxy-6R-S-cysteinylglycyl-7,9-trans-11,14-cis-eicosatetraenoic acid5-7; and LTE4, 5S-hydroxy-6R-S-cysteinyl-7,9-trans-11,14-cis-eicosatetraenoic acid.8 That efforts to decrease the generation of the leukotriene compounds could have a significant effect in down-regulating a variety of inflammatory events has been strongly suggested by several types of data developed over the past 5 years, with regard to the breadth of proinflammatory effects manifested by these compounds, indications that a variety are mediated via specific receptors that do not recognize other naturally-occurring compounds, an expanding knowledge of the inflammatory cell types which serve as sources for the leukotrienes, and the demonstration that leukotrienes are recoverable from complex biological fluids in both in vivo models of inflammation and human disease. Although there is potential for antagonizing the biological effects of each leukotriene at the end-organ receptor level, the present discussion will focus mainly on regulation of leukotriene biosynthesis as an anti-inflammatory therapeutic approach. Furthermore, the potential of dietary alteration as an adjunct to developing pharmacotherapeutic inhibitors of the 5-lipoxygenase pathway will be specifically considered.
Recipient of Allergic Diseases Academic Award AI-00399 from the National Institutes of Health
Recipient of a Saltwell Fellowship, Royal College of Physicians, London, U.K.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
P. Borgeat, M. Hamberg, and B. Samuelsson, Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases, J. Biol. Chem. 251:7816 (1976), and correction: 252: 8772 (1977).
E.J. Goetzl, A role for endogenous mono-hydroxy-eicosatetraenoic acids (HETEs) in the regulation of human neutrophil migration, Immunology. 40: 709 (1980).
P. Borgeat and B. Samuelsson, Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187, Proc. Natl. Acad. Sci. USA. 76: 2148 (1979).
R.C. Murphy, S. Hammarstr’óm, and B. Samuelsson, Leukotriene C: a slow reacting substance from purine mastocytoma cells, Proc. Natl. Acad. Sci. USA. 76: 4275 (1979).
R.A. Lewis, K.F. Austen, J.M. Drazen, D.A. Clark, A. Marfat, and E.J. Corey, Slow reacting substances of anaphylaxis: identification of leukotriene C-1 and D from human and rat sources, Proc. Natl. Acad. Sci. USA. 77: 3710 (1980).
L. Örning, S. Hammarstr’óm, and B. Samuelsson, Leukotriene D: a slow reacting substance from rat basophilic leukemia cells, Proc. Natl. Acad. Sci. USA. 77: 2014 (1980).
H.R. Morris, G.W. Taylor, P.J. Piper, and J.R. Tippins, Structure of slow reacting substance of anaphylaxis from guinea pig lung, Nature. 285: 104 (1980).
R.A. Lewis, J.M. Drazen, K.F. Austen, D.A. Clark, and E.J. Corey, Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis geometry for biological activity, Biochem. Biophys. Res. Commun. 96: 271 (1980).
W.E. Brocklehurst, The release of histamine and formation of a slow reacting substance of anaphylaxis (SRS-A) during anaphylactic shock, J. Physiol. 151: 416 (1960).
J.M. Drazen, R.A. Lewis, S.I. Wasserman, R.P. Orange, and K.F. Austen, Differential effects of a partially purified preparation of slow reacting substance of anaphylaxis on guinea pig tracheal spirals and parenchymal strips, J. Clin. Invest. 63: 1 (1979).
J.M. Drazen, K.F. Austen, R.A. Lewis, D.A. Clark, G. Goto, A. Marfat, and E.J. Corey, Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro, Proc. Natl. Acad. Sci. USA. 77: 4354 (1980).
J.M. Drazen C.S. Venugopalan, K.F. Austen, F. Brion, and E.J. Corey, Effects of leukotriene E on pulmonary mechanics in the guinea pig, Am. Rev. Respir. Dis. 125: 290 (1982).
A.G. Leitch, E.J. Corey, K.F. Austen, and J.M. Drazen, Indomethacin potentiates the pulmonary response to aerosol leukotriene C4 in the guinea pig, Amer. Rev. Respir. Dis. 128: 639 (1983).
G. Smedeg-rd, P. Hedqvist, S.-E. Dahlén, B. Revenus, S. Hammarstr’m, and B. Samuelsson, Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey, Nature. 295: 327 (1982).
J.M. Drazen and K.F. Austen, Effects of intravenous administration of slow reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin F2a on pulmonary mechanics in the guinea pig, J. Clin. Invest. 53: 1679 (1974).
J.M. Drazen, R.A. Lewis, K.F. Austen, and E.J. Corey, Pulmonary pharmacology of the SRS-A leukotrienes, in: “Leukotrienes and Prostacyclin,” F. Berti, G. Folco, and G Velo, eds., Plenum Press, New York (1983).
M.C. Holroyde, R.E.C. Altounyan, M. Cole, M. Dixon, and E.V. Elliot, Bronchoconstriction produced in man by leukotriene C and D, Lancet. 2: 17 (1981).
J.W. Weiss, J.M. Drazen, N. Coles, E.R. McFadden, Jr., P.F. Weller, E.J. Corey, R.A. Lewis, and K.F. Austen, Bronchoconstrictor effects of leukotriene C in humans, Science. 216: 196 (1982).
J.W. Weiss, J.M. Drazen, E.R. McFadden, Jr., P.F. Weller, E.J. Corey, R.A. Lewis, and K.F. Austen, Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy, J. Amer. Med Assoc. 249: 2814 (1983).
Z. Marom, J.H. Shelhamer, M.K. Bach, D.R. Morton, and M. Kaliner, Slow-reacting substances, leukotrienes C4 and D4, increase the release of mucus from human airways in vitro, Am. Rev. Respir. Dis. 126: 449 (1982).
S.J. Coles, K.H. Neill, L.M. Reid, K.F. Austen, Y. Nii, E.J. Corey, and R.A. Lewis, Effects of leukotrienes C4 and D4 on glycoprotein and lysozyme secretion by human bronchial mucosa, Prostaglandins. 25: 155 (1983).
S.-E. Dahlén, J. Bjork, P. Hedqvist, K.-E. Arfors, S. Hammarström, J.-A. Lindgren, and B. S.muelsson, Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response, Proc. Natl. Acad. Sci. USA. 78: 3887 (1981).
N.A. Soter, R.A. Lewis, E.J. Corey, and K.F. Austen, Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4, and LTB4) in human skin, J. Invest. Derm. 80: 115 (1983).
F. Michelassi, L. Landa, R.D. Hill, E. Lowenstein, W.D. Watkins, A.J. Petkau, and W.M. Zapol, Leukotriene D4: a potent coronary artery vasoconstrictor associated with impaired ventricular contraction, Science. 217: 841 (1982).
M.A. Pfeffer, J.M. Pfeffer, R.A. Lewis, E. Braunwald, E.J. Corey, and K.F. Austen, Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat, Am. J. Physiol. 244: H628 (1983).
J. Bittl, M.A. Pfeffer, R.A. Lewis, J.M. Pfeffer, J.S. Ingwall,and K.F. Austen, Mechanism of the negative ionotropic action of leukotrienes C4 and D4 on the isolated rat heart, J. Amer. College Cardiol. 3: 503 (1984).
K.F. Badr, C. Baylis, J.M. Pfeffer, M.A. Pfeffer, R.J. Soberman, R.A. Lewis, K.F. Austen, E.J. Corey, and B.M. Brenner, Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat, Circ. Res. 54: 492 (1984).
P. Sirois, S. Roy, and P. Borgeat, The lung parenchymal strip as a sensitive assay for leukotriene 84, Prostaglandins Med. 6: 153 (1981).
E.J. Goetzl and W.C. Pickett, The human polymorphonuclear leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs), J. Immunol. 125: 1789 (1980).
R.A. Lewis, J.M. Drazen, E.J. Corey, and K.F. Austen, Structural and functional characteristics of the leukotriene components of slow reacting substance of anaphylaxis (SRS-A), in: “SRS-A and the Leukotrienes,” P.J. Piper, ed., John Wiley and Sons, London (1981).
R.L. Hoover, M.L. Karnovsky, K.F. Austen, E.J. Corey, and R.A. Lewis, Leukotriene B4 action on endothelium mediates augmented neutrophil/endothelial adhesion, Proc. Natl. Acad. Sci. USA. 81: 2191 (1984).
D. Atluru and J.S. Goodwin, Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; LTB4 induces an OKT8(+), radiosensitive suppressor cell from resting human OKT8(-) T cells, J. Clin. Invest. (in press).
D.G. Payan and E.J. Goetzl, Specific suppression of human T lymphocyte function by leukotriene 84, J. Immunol. 131: 551 (1983).
M.P. Rola-Plezczynski, P. Borgeat, and P. Sirois, Leukotriene B4 induces human suppressor lymphocytes, Biochem. Biophys. Res. Commun. 198: 1531 (1982).
R.A. Lewis, J.M. brazen, K.F. Austen, M. Toda, F. Brion, A. Marfat, and E.J. Corey, Contractile activities of structural analogs of leukotrienes C and D: role of the polar substituents, Proc. Natl. Acad. Sci. USA. 78: 4579 (1981).
S. Krilis, R.A. Lewis, E.J. Corey, and K.F. Austen, Specific binding of leukotriene C4 on a smooth muscle cell line, J. Clin. Invest. 72: 1516 (1983).
S. Krilis, R.A. Lewis, E.J. Corey, and K.F. Austen, Specific binding of leukotriene C4 to ileal segments and subcellular fractions of ileal smooth muscle, Proc. Natl. Acad. Sci. USA. 81: 4529 (1984).
S.S. Pong, R.N. DeHaven, F.A. Kuehl, Jr., R.W. Egan, Leukotriene C4 binding to rat lung membranes, J. Biol. Chem. 258: 9616 (1983).
G.K. Hogaboom, S. Mong, H.-L. Wu, and S. Crooke, Peptidoleukotrienes: distinct receptors for leukotrienes C4 and D4 in the guinea pig lung, Biochem. Biophys. Res. Commun. 116: 1136 (1983).
R.F. Bruns, W.J. Thomsen, and T.A. Pugsley, Binding of leukotrienes C4 and D4 to membranes from guinea pig lung: regulation by ions and guanine nucleotides, Life Sci. 33: 645 (1983).
S.S. Pong and R.N. DeHaven, Characterization of a leukotriene D4 receptor in guinea pig lung, Proc. Natl. Acad. Sci. USA. 80: 7415 (1983).
S. Krilis, R.A. Lewis, and K.F. Austen, Classes of receptors for the sulfidopeptide leukotrienes, in: “Icosanoids and Ion Transport,” P. Braquet and B. Samuelsson, eds., Raven Press, New York (in press)
B.J. Ballermann, R.A. Lewis, E.J. Corey, K.F. Austen, and B.M. Brenner, Identification of leukotriene C4 (LTC4) receptors in isolated rat renal glomeruli, Clin. Res. 32: 440A (1984).
E.J. Goetzl and W.C. Pickett, Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B, J. Exp. Med. 153: 482 (1981).
R.A. Lewis, E.J. Goetzl, J.M. Drazen, N.A. Soter, K.F. Austen, and E.J. Corey, Functional characterization of synthetic leukotriene B and its stereochemical isomers, J. Exp. Med. 154: 1243 (1981).
A.W. Ford-Hutchinson, M.A. Bray, F.M. Cunningham, E.M. Davidson, and M.J.H. Smith, Isomers of LTB4 posess different biological potencies, Prostaglandins 21: 143 (1981).
D.W. Goldman and E.J. Goetzl, Specific binding of leukotriene B4 to receptors on human polymorphonuclear leukocytes, J. Immunol. 129: 1600 (1982).
D.W. Goldman and E.J. Goetzl, Selective transduction of human polymorphonuclear leukocyte functions by subsets of receptors for leukotriene B4, J. Allergy Clin. Immunol. (in press).
P.F. Weller, C.W. Lee, D.W. Foster, E.J. Corey, K.F. Austen, and R.A. Lewis, Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4, Proc. Natl. Acad. Sci. USA. 80: 7626 (1983).
C.W. Lee, R.A. Lewis, A.I. Tauber, M. Mehrotra, E.J. Corey, and K.F. Austen, The myeloperoxidase-dependent metabolism of leukotrienes C4, D4, and E4 to 6-trans-leukotriene B4 diastereoisomers and the subclass-specific S-diastereoisomeric sulfoxides, J. Biol. Chem. 258: 15004 (1983).
A.O. Fels, N.A. Pawlowski, E.B. Cramer, T.K.C. King, Z.A. Cohn, and W.A. Scott, Human alveolar macrophages produce leukotriene B4, Proc. Natl. Acad. Sci. USA. 79: 7866 (1982).
T.R. Martin, L.C. Altman, R.K. Albert, and W.R. Henderson, Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung, Amer. Rev. Respir. Dis. 125: 106 (1984).
P. Godard, M. Damon, F.B. Michel, E.J. Corey, K.F. Austen, and R.A. Lewis, Leukotriene B4 production from human alveolar macrophages, Clin. Res. 31: 548A (1983).
J.D. Williams, J.K Czop, and K.F. Austen, Release of leukotrienes by human monocytes on stimultion of their phagocytic receptor for particulate activators, J. Immunol. 132: 3034 (1984).
D.W. MacGlashan, R. Schleimer, S.P. Peters, E.S. Schulman, G.K. Adams, H.H. Newball, and L.M. Lichtenstein, Generation of leukotrienes by purified human lung mast cells, J. Clin. Invest. 70: 747 (1982).
S.P. Peters, D.W. MacGlashan, E.S. Schulman, R.P. Schleimer, E.C. Hayes, J. Rokach, N.F. Adkinson and L.M. Lichtenstein, Arachidonic acid metabolism in purified human lung mast cells, J. Immunol. 132: 1972 (1984).
T. Shimizu, O. RRdmark, and B. Samuelsson, Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid, Proc. Natl. Acad. Sci. USA. 81: 689 (1984).
Rddmark, C. Malmsten, B. Sanuelssson, G. Goto, A. Marfat, and E.J. Corey, Leukotriene A: isolation from human polymorphonuclear leukocytes, J. Biol. Chem. 255: 11828 (1980).
A.L. Maycock, M.S. Anderson, D.M. DeSousa, and F.A. Kuehl, Jr., Leukotriene A4: preparation and enzymatic conversion in a cell-free system to leukotriene B4, J. Biol. Chem. 257: 13911 (1982).
M.K. Bach, J.R. Brashler, and D.R. Morton, Jr., Solubilization and characterization of the leukotriene C4 synthetase of rat basophil leukemia cells: a novel, particulate glutathione-S-transferase, Arch. Biochem. Biophys. 230: 455 (1984).
R.A. Lewis and K.F. Austen, The biologically active leukotrienes: biosynthesis, metabolism, receptors, functions, and pharmacology, J. Clin. Invest. 73: 889 (1984).
E.J. Corey, H. Park, A. Barton, and Y. Nii, Synthesis of three potential inhibitors of the biosynthesis of leukotrienes A-E, Tetrahedron Lett. 21: 4243 (1980).
E. Razin, L.C. Romeo, S. Krilis, F.-T. Liu, R.A.Lewis, E.J. Corey, and K.F. Austen, An analysis of the relationship between 5-lipoxygenase product generation and the secretion of preformed mediators from mouse bone marrow-derived mast cells, J. Immunol. 133: 938 (1984).
M.K. Bach, J.R. Brashler, H.W. Smith, F.A. Fitzpatrick, F.F. Sun, and J.C. Maguire, 6,9-deepoxy-6,9-(phenylimino)-a638_ prostaglandin Il (U-60,257), a new inhibitor of leukotriene C and D synthesis: in vitro studies, Prostaglandins 23: 759 (1982).
B.M. Weichman, M.A. Wasserman, D.A. Holden, R.R. Osborn, D.F. Woodward, T.W. Ku, and J.G. Gleason, Antagonism of the pulmonary effects of the peptidoleukotrienes by a leukotriene D4 analog, J. Pharmacol. Exp. Ther. 227: 700 (1983).
R.C. Murphy, W.C. Pickett, B.R. Culp, and W.E.M. Lands, Tetraene and pentaene leukotrienes: selective production from murine mastocytoma cells after dietary manipulation, Prostaglandins. 22: 613 (1981).
J.D. Prickett, D.R. Robinson, and A.D. Steinberg, Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW F1 mice, J. Clin. Invest. 68: 556 (1981).
J.D. Prickett, D.W. Trentham, and D.R. Robinson, Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen, J. Immunol. 132: 725 (1984).
E.J. Corey, C. Shih, and J.R. Cashman, Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis, Proc. Natl. Acad. Sci. USA 80: 3581 (1983).
R.P.Orange, M.D. Valentine, and K.F. Austen, Antigen-induced release of slow reacting substance of anaphylaxis (SRS-Arat) in rats prepared with homologous antibody, J. Exp. Med. 127: 767 (1968).
A.G. Leitch, T.H. Lee, E.W. Ringel, J.D Prickett, D.R. Robinson, S.G. Pyne, E.J. Corey, J.M. Drazen, K.F. Austen, and R.A. Lewis, Immunologically-induced generation of tetraene and pentaene leukotrienes in the peritoneal cavities of menhaden-fed rats, J. Immunol. 132: 2559 (1984).
T.H. Lee, J.-M. Mencia-Huerta, C. Shih, E.J. Corey, R.A. Lewis, and K.F. Austen, Characterization and biologic properties of 5,12-dihydroxy derivatives of eicosapentaenoic acid, including leukotriene B5 and the double lipoxygenase product, J. Biol. Chem. 259: 2383 (1984).
S. Hammarström, Conversion of 14C-labeled eicosapentaenoic acid (N-3) to leukotriene C5, Biochim. Biophys. Acta. 663: 575 (1981).
S.-E. Dahldn, P. Hedqvist, and S. Hammarström, Contractile activities of several cysteine-containing leukotrienes in the guinea pig lung strip, Eur. J. Pharmacol. 86: 207 (1982).
T.H. Lee, R.A. Lewis, D.R. Robinson, J.M. Drazen, and K.F. Austen, The effects of a diet enriched in menhaden fish oil on the pulmonary response to antigen challenge, J. Allergy Clin. Immunol. 73: 150 (1984).
E.A. Ham, D.D. Soderman, M.E. Zanetti, H.W. Dougherty, E. McCauley, and F.A. Kuehl, Jr., Inhibition by prostaglandins of leukotriene B4 release from activated neutrophil, Proc. Natl. Acad. Sci. USA. 80: 4349 (1983).
L. Levine, R. Morgan, R.A. Lewis, K.F. Austen, D.A. Clark, A. Marfat, and E.J. Corey, Radioimmunoassay of the leukotrienes of slow reacting substance of anaphylaxis (SRS-A), Proc. Natl. Acad. Sci. USA. 78: 7692 (1981).
E.C. Hayes, D.L. Lombardo, Y. Girard, A.L. Maycock, J. Rokach A.S. Rosenthal, R.M. Young, R.W. Egan, and H.J. Zweerink, Measuring leukotrienes of slow reacting substance of anaphylaxis: development of specific radioimmunoassay, J. Immunol. 131: 429 (1983).
K. Ochi, T. Yoshimoto, S. Yamamoto, K. Taniguchi, and T. Miyamoto, Arachidonate 5-lipoxygenase of guinea pig peritoneal polymorphonuclear leukocytes, J. Biol. Chem. 258: 5754 (1983).
R.J. Soberman, R.A. Lewis, E.J. Corey, and K.F. Austen, The characterization of two lipoxygenases from the human PMN, Fed. Proc. 43: 1879 (1984).
T.H. Lee, J.-M. Mencia-Huerta, C. Shih, E.J. Corey, R.A. Lewis, and K.F. Austen, Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophoreactivated human neutrophils, J. Clin. Invest. (in press).
S. Fischer, C.V. Schacky, W. Siess, T. Strasser, and P.C. Weber, Uptake, release and metabolism of docosahexaenoic acid in human platelets and neutrophils, Biochem. Biophys. Res. Commun. 120: 907 (1984).
H.O. Bang, and J. Dyerberg, Lipid metabolism and ischemic heart disease in Greenland Eskimoes, Adv. Lipid Res. 3: 1 (1980).
H. Herxheimer and O. Shaefer, Asthma in Canadian Eskimoes, N. Engl. J. Med. (correspondence) 291: 1419 (1974).
J. Dyerberg, H.O. Bang, G. Stoffersen, S. Moncada, and J.R. Vane, Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis, Lancet. 1: 117 (1978).
P. Needleman, A. Raz, N.S. Minkes, A. Ferendelli, and H. Sprecher, Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties, Proc. Natl. Acad. Sci. USA. 76: 944 (1979).
G.H.R. Rai, E. Radha, and J.G. White, Effect of docosahexaenoic acid (DHA) on arachidonic acid metabolism and platelet function, Biochem. Biophys. Res. Commun. 117: 5498 (1983).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Plenum Press, New York
About this chapter
Cite this chapter
Lewis, R.A., Lee, T.H., Austen, K.F. (1985). Pharmacologic Modulation of Leukotriene Biosynthesis by Incorporation of Alternative Unsaturated Fatty Acids (20:5 and 22:6). In: Samuelsson, B., Berti, F., Folco, G.C., Velo, G.P. (eds) Drugs Affecting Leukotrienes and Other Eicosanoid Pathways. NATO ASI Series, vol 95. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7841-9_6
Download citation
DOI: https://doi.org/10.1007/978-1-4684-7841-9_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-7843-3
Online ISBN: 978-1-4684-7841-9
eBook Packages: Springer Book Archive