Leukotrienes and prostanoids in health and disease (advances in prostaglandin, thromboxane and leukotriene research, vol. 16)

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Book reviews

Contemporary Themes in Biochemistry, Vol. 6, by O.L. Kon, M . C . M . Chung, P . L . H . Hwang, S.F. Leong, K.H. Loke, P. Thiyagarajah and P . T . H . Wong. Cambridge University Press, Cambridge, 1987, 715 p., £ 30 This book corresponds to the abstracts of the 300 or so papers presented at the 4th Federation of Asian and Oceanian Biochemists Congress in Singapore (Nov. 30-Dec. 5, 1986). It is no more and no less than the abstracts book delivered at an international meeting and its use for the standard biochemist is not obvious... Perhaps a research scientist in sociology of science might be interested in seeing how biochemistry and molecular biology is now spreading! A. Danchin

Leukotrienes and Prostanoids in Health and Disease (Advances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 16), by U. Zor, Z. Naor and F. Kohen. Raven Press, New York, 1986, 423 p., US$ 44.50 The 16th volume of the Advances in Prostaglandin, Thromboxane and Leukotriene Research series is based on lectures presented at the International Conference on Leukotrienes and Prostanoids in Health and Disease, which was held in Rehovot, Israel, in October, 1985. It is divided into 7 chapters: Chapter 1 : Presentation of 3 studies on the regulation of lipoxygenases (LO), the main enzymes in leukotriene (LT) production. Samuelsson et al. (Sweden) provide new information on human leukoc_~e 5-1ipoxygenase. The fraction purified to near homogeneity has a M r of 80 kDa and is of great instability. It has both 5-LO and LTA4 synthetase activities, controlled by a multicomponent regulatory system, unique among the LO studied to date, and consistent with their proposed role in inflammation and hypersensitivity.Yamamoto el al. (Japan) emphasize the versatile activities of 12- and 5-LO of porcine leukocytes: broad substrate specificity and catalysis of different types of reactions. Lewis and Austen (U.S.A.) review the regulation of LT biosynthesis by N-3 fatty acids, cytokines and stimuli for cell activation. They show the complexity of the factors that could modulate the in vivo regulation of LT biosynthesis and could control their bioavailable concentration for participating in the pro-inflammatory response in the microenvironment. Chapter 2 describes new antagonists and inhibitors of leukotriene action and production. Three studies received special emphasis. Rokach et al. (U.S.A.) report the design and the development of a selective orally active LTD 4 receptor antagonist L649,923. This compound was shown to be a competitive antagonist of LTD 4 binding in guinea pig lung and ileum preparations, whereas it was non-competitive in guinea pig trachea, suggesting

differences in receptor subtypes and/or mechanisms between these two tissues. Ackerman et al. (U.S.A.) using two mouse inflammatory models which are sensitive to LO inhibitors (arachidonateoinduced ear edema and con. tact sensitivity to DFNB models) dissect the effects of LO and cyclooxygenase (CO) inhibitors in relation to the successive phases of the inflammation (edema and cellular inf'dtration) and show the important involvement of 5-L0 products. Tischler et al. (U.S.A.) describe a novel and potent dual 5-LO-CO inhibitor L652,343, already undergoing clinical evaluation. Chapter 3 is devoted through studies to discussions of the chemistry and the biological activities of lipoxins (LX), new members of the family. Samuelsson et ai. (Sweden), who isolated and identified these dihydroxy. tetraene metabolites of arachidonate from human leukocytes, present new data on the biochemistry of LXB and of two natural isomers. Morris and Wishka (U.S.A.) describe a total synthesis of LXB. Rokach et al. (U.S.A.) show that from 5,6 epoxide or 5,15 diHPETE, all isomers of LXA and LXB, could be generated non-enzymatically and contest the large spectrum of biological activities of LX. Chapter 4 represents the most important part of this volume, and discusses various aspects of allergy, immunology and inflammation in relation to eicosanoids. Parker (U.S.A.) explores the abundant and contradictory literature. He emphasized the effects obtained with the 5-LO derivatives and the eventual role of LTB4 as a mediator of T cell function. One can regret the exclusion from this excellent review of 12- and 15-L0 derivatives. Razin and Baranes (Israel) carrying on their studies on thrombin-mediated activations show that thrombin rapidly triggers lysozyme release from human PMN without concomitant activation of the 5-L0 pathway. Jakschik et al. (U.S.A.) found that macrophages and possibly PMN modulate and contribute to immediate hypersensitivity reactions. Antigen stimulation of sensitized mast cells in vitro in the presence of macrophages showed that the latter contribute prostaglandins and modulate the 5-LO products. Their decrease appeared to be due to active oxygen species and may serve as a negative feedback mechanism to maintain relative homeostasis. Bromberg et al. (Israel) describe a macrophage derived cell free system capable of generating 0 2 and H202 when activated by fatty acids and some anionic detergents in the presence of NADPH. They isolated two components of this system and analyzed their respective properties. Gorman et al. (U.S.A.) expose HL-60 cells (promyelocytic cell lines) for 6 days to a combination of DMSO and dexamethasone and observed induction of myeloid differentiation and of specific binding for LTB 4, correlated with the ability to chemotax in response to LTB4. Interestingly, undifferentiated and myeloid differentiated HL-60 cells can, at 37°C, incorporate LTB 4 into phospholipids and neutral lipid species. This model is proposed for the study of LTB 4 receptor binding, processing and gene expression. Braquet (France), carrying on exciting studies on specific antagonists of PAF-acether, gives here a complete and clear synthesis of the data on the antagonistic

Book reviews

tctivity of ginkgolides and their potential clinical applica:ions: mainly in asthma, acute respiratory distress syndrome, cold urticaria in which PAF-acether seems to play key role. The author reports promising effects of these aatural inhibitors of PAF-acether observed in various types of shock and also as graft protectors during organ transplantation in combination with immunosuppres~ive agents. Patron et al. (Italy) report measurements of urinary prostanoids in chronic glomerular disease (decrease of 6kPGFI~) and in systemic lupus erythematosus where the group with active renal lesions had lower 6kPGF~ and higher TXB 2 urinary excretions than the group with inactive lesions. Foegh et al. (U.S.A.), carrying on their clinical and experimental studies of allograft rejection, confirm here that urine TXB 2 is an early indicator of kidney rejection and found no correlation in 9 transplant patients between serum ~,-interferon and urine TXB 2. Chapter 5 concerns some neuroendocrine functions. Lapetina et al. (U.S.A.) report already published results on the turnover of inositol phospholipids in stimulated human platelets. Naor et al. (Israel) discusses the sequence of events mediating the neurohormone action on pituitary hormone release with emphasis on GnRI-I action and proposes a mechanism of action of GnRH involving 5-LO products (5-HETE and LTC4). Dray et al. (France) present new data concerning the properties of the hypothalamic PGE 2 receptor mainly in relation with estrus cycle in the rat and the involvement of LO products (12-HETE, 5-HETE and LTC4) on the release of LHRH. Grossman et al. (Israel) study the arachidonate metabolism in perfused sheep testes where 15-HETE and 6kPGF~ are the major products and in sperm where 15-LO products were detected. The inhibitory effect of NDGA on respiration and motility of the ram sperm cell suggests that 15-LO products may play an import~t~,'..: physiological role. Chapter 6 deals with the cardiovascular system. Piper and Stanton (U.K.) study the actions of LT in coronary and intracranial circulations of the pig and on isolated cerebral arteries. The effects obtai~led suggest that LT could be released in vivo from cerebral arterial walls in cerebrovascular diseases and the local vasotoxic effects, such as spasm or increased permeability, could result in cerebral, ischema or edema. Peskar et al. (F.R.G.) 0bser-¢e the release and analyze the effects of sulfidopeptido-LT in isolated anaphylactic guinea pig hearts, isolated perfused rabbit kidneys and rat gastric mucosa. Zor et ai. (Israel) show that the prime effect of membrane bound immune complexes is an increase of free intracellular C a 2+ followed by a production and release of LT. When this occurs in the coronary arteries, it may lead, in the intact animal, to cardiac myolysis. Hintze

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et al. (U.S.A.) investigate the effects of LTD4 on large

coronary arteries in the conscious dog and find no effect, in contrast to the dramatic large coronary artery constriction following the injection of U-46619, an endoperoxide analog. These resalts exclude a critical role of LT in coronary vasospasm. Feuerstein (U.S.A.) observed, through the liter~,ture, that all major components of the cardiovascular system are affected by the 5-LO products, including small and large blood vessels, cardiac and coronary functions, the microcirculation and systemic reflexes. Green and Vesterqvist (Sweden) investigate through G C - M S techniques the in vivo synthesis of TXA 2 and PGI 2 in normal subjects, following various drugs and during synthetic arterial graft surgery, after total artificial heart implantation and during acute myocardial infection. The measurements of urine 2,3 dinor-TXB 2 and 2,3 dinor-6kPGFt~ are excellent indicators of the in vivo synthesis of the parent compound. Chapter 7 concerns analysis and metabolism problems. Yalow (U.S.A.) observes that RIA methodology finds its application for any organic substance of biological interest. However, she insists on the necessity of rigorous validations, and her presentation is a guide for optimizing RIA procedure. Levine (U.S.A.) through his high expertise in the field of LT RIA, insists on the necessity of a separation of the serologically active species before the LT can be quantitated. Murphy et ai. (U.S.A.) observe that after HPLC, RIA and mass spectrometry, LTD 4 and not LTC4 is present in human lung lavage fluid collected during mechanically-assisted ventilation of an infant with chronic lung disease. Frolich et al. (F.R.G.) compare the advances in the analysis of eicosanoids by enzyme-linked immunoassays (ELISA) and GC/MS/MS. The ELISA is as performant as classical RIA and ~he emergence of triple quadruple mass spectrometry is a valuable new tool in trace analysis. Nugteren (Netherlands) describes a sensitive UV spectroscopy technique coupled to HPLC for the measurement of LO products (eicosa- and octadecanoids). Its application to blood platelcts, neutrophils and skin epidermis shows the diversity c,'_."the metabolic profiles. Hammarstrom et al. (Sweden) finishes the chapter with the analysis of the metabolism and excretion of cysteinyl-LTs. In summary, as usual in the previous volumes of this series, too many aspects of the research concerning these active lipi~ are presented here, through a pot-pourri of reviews, original and already published data. However, in spite of this restriction, it offers the opportunity to realize the importance of the research in the field of leukotrienes. F. Dray