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Metabolism of Arachidonic Acid by Isolated Lung Cells and Transcellular Biosynthesis of Thromboxanes

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Cell-Cell Interactions in the Release of Inflammatory Mediators

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 314))

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Abstract

Harkavy1 was the first to report that an alcohol-soluble extract of sputum from allergic asthmatic patients contained an agent which provoked spasms of cat and rabbit intestines in vitro. Few years later, von Euler2 and Goldblatt3 showed that extracts from human prostate gland and seminal vesicles decreased the blood pressure and stimulated the smooth muscles of the uterus. The compounds were designated as prostaglandins2. A new area of research on arachidonic acid metabolism started by the characterization of prostaglandins E and F by Bergström and Sjövall4,5. The final structures of PGE1 PGF1α and PGF1β were elucidated later6. The thromboxanes were first described as the rabbit aorta contracting substance (RCS) by Piper and Vane7. Hamberg et al.8 showed that RCS corresponded to the unstable thromboxane A2. Another line of investigations focused on the nature of substances causing a slowly developing and long-lasting contraction of guinea pig jejunum in vitro9. This substance called slow reacting substance (SRS) was shown to be released during the antigen-antibody reaction in guinea pig anaphylaxis and later designated as slow reacting substances of anaphylaxis (SRS-A). SRS-A were purified and characterized for the first time by Morris et al.10. The first product of the SRS-A has been identified as leukotriene C by Murphy et al.11 and Morris et al.12. The two other components of SRS-A were demonstrated to be the leukotriene D4 (LTD4) formed through cleavage of the γ-glutamyl moiety of the gluthathione side chain of LTC4 13,15 and the leukotriene E4 (LTE4) formed through the cleavage of the glycine residue from the peptide chain of LTD4 14,16. Leukotriene B4 (LTB4) was originally isolated by Borgeat and Samuelsson, in incubates of rabbit PMNL17 or human PMNL18 stimulated with arachidonic acid and calcium ionophore.

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Authors and Affiliations

  1. Department of Pharmacology Faculty of Medicine, University of Sherbrooke, Sherbrooke (P.Q.), Canada, J1H 5N4

    Karim Maghni, Chantal Robidoux, Johanne Laporte, Annie Hallée, Johanne Carrier & Pierre Sirois

  2. Inflammation et Immunologie-Rhumatologie CHUL, Quebec, Canada, G1V 4G2

    Pierre Borgeat

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  1. Karim Maghni
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  1. New York Medical College, Valhalla, New York, USA

    Patrick Y.-K. Wong

  2. Harvard Medical School, Boston, Massachusetts, USA

    Charles N. Serhan

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Maghni, K. et al. (1991). Metabolism of Arachidonic Acid by Isolated Lung Cells and Transcellular Biosynthesis of Thromboxanes. In: Wong, P.YK., Serhan, C.N. (eds) Cell-Cell Interactions in the Release of Inflammatory Mediators. Advances in Experimental Medicine and Biology, vol 314. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6024-7_19

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