Douglas R. Morton

Allergic pulmonary reactions in vivo lead to airway constriction and mucous secretion, whereas in vitro lung anaphylaxis lead to mediator release and increased mucous glycoprotein secretion from cultured human airways. Using quantitation of radiolabeled mucous glycoprotein from cultured airways as a model for mucous release, the effects of two leukotrienes, LTC4 and LTD4, were assessed. BOth biosynthetic and synthetic LTC4 and LTD4 produced dose-related increases in mucous production at concentrations of 1 to 1,000 units/ml (20 to 20,000 pg [LTD4] and 24 to 24,000 pg [LTC4]/ml). These enhancing actions were seen in 11 of 11 lung cultures, and were significantly prevented by the specific SRS-A antagonist FPL 55712. Therefore, LTC4 and LTD4, two major components of the allergic mediator SRS-A, are potent mucous secretagogues and may possibly contribute to the mucous secretion observed during allergic reactions in vitro and in vivo.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular photochemistry. L. Molecular photochemistry of alkanones in solution. .alpha.-Cleavage, hydrogen abstraction, cycloaddition, and sensitization reactionsNicholas J. Turro, J. Christoper Dalton, Keith Dawes, George Farrington, Richard Hautala, Douglas Morton, Mark Niemczyk, and Neil SchoreCite this: Acc. Chem. Res. 1972, 5, 3, 92–101Publication Date (Print):March 1, 1972Publication History Published online1 May 2002Published inissue 1 March 1972https://pubs.acs.org/doi/10.1021/ar50051a002https://doi.org/10.1021/ar50051a002research-articleACS PublicationsRequest reuse permissionsArticle Views530Altmetric-Citations169LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Acetyl glyceryl ether phosphorylcholine (AGEPC) and leukotriene B4 (LTB4) induce concentration-dependent neutrophil aggregation. On a molar basis, LTB4 is approximately 10 to 100 times more potent than AGEPC. AGEPC-induced aggregation is attenuated by two inhibitors of arachidonate lipoxygenation, eicosatetraynoic acid and nordihydroguaiaretic acid, and to a lesser extent by the cyclooxygenase inhibitor, indomethacin. LTB4-induced aggregation is not readily reduced by the above inhibitors of arachidonic acid metabolism. Reverse phase high performance liquid chromatography, coupled with selective ion gas chromatography/mass spectrometry, shows that AGEPC stimulates neutrophils to synthesize sufficient LTB4 to account for the AGEPC response. In addition, the rate of LTB4 biosynthesis in response to AGEPC correlates well with the rate of AGEPC- and/or LTB4-induced neutrophils aggregation, and desensitization experiments indicate that AGEPC and LTB4 cross-desensitize. These data suggest that AGEPC-induced neutrophil aggregation may be mediated by LTB4.

Chemical analysis of intact leukotriene A4 showed that vertebrate albumins prolonged its aqueous half-life. At pH 7.4, leukotriene A4 hydrolyzed by first order reaction kinetics with rate constants inversely proportional to the albumin concentration. The stabilizing effect of albumin varied quantitatively among different species. Certain agents, such as warfarin, that interact with the site I binding region of albumin reversed its stabilizing effect. Sequestration and exposure of leukotriene A4 to a hydrophobic, alkaline microenvironment of albumin would account for the results. The amino acid sequences Lys-Ala-Trp-Ala-Val-Ala-Arg from residues 211-217 of human albumin or Lys-Ala-Trp-Ser-Val-Ala-Arg from residues 210-216 of bovine albumin are compatible with this requirement. The persistence of leukotriene A4 in the presence of albumin confirms and extends our recent observations on its uniform and predictable influence on eicosanoid stability. The significance of this influence is uncertain; however, albumin can no longer be viewed as inert considering its capacity to modify the stability of several, structurally diverse eicosanoids.