Journal article

Publication year: 2010

Pages: 1088-1098

Journal: European Respiratory Journal

Volume number: 36

Issue number: 5

ISSN: 0903-1936

eISSN: 1399-3003

Open access status: Bronze

DOI Link: https://doi.org/10.1183/09031936.00000309

Publisher: European Respiratory Society

Abstract: 

Lipoxygenase, cyclo-oxygenase and cytochrome P450 (CYP) products of arachidonic acid (AA) are implicated in pulmonary vasoregulation. The CYP-mediated epoxyeicosatrienoates (EETs) have been described previously as the predominant eicosanoids in human lungs upon stimulation with the Ca2+ ionophore A23187. In this study, we challenged perfused human lungs with two microbial agents: Escherichia coli haemolysin (ECH) and formylmethionyl-leucyl-phenylalanine (fMLP).

Both stimuli elicited pronounced generation of leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostanoids (PTs) and EETs/dihydroxyeicosatrienoic acids (DHETs), as assessed by liquid chromatography-mass spectrometry, paralleled by pulmonary artery pressor response and lung oedema formation. The maximum buffer concentrations of EETs/DHETs surpassed those of LTs plus HETEs and PTs by a factor of four (ECH) or three (AA/fMLP). Dual 5-lipoxygenase/cyclo-oxygenase inhibition caused pronounced reduction of AA/fMLP-induced LT/PT synthesis and oedema formation but only limited attenuation of pulmonary vasoconstriction, while inhibition of CYP epoxygenase clearly attenuated AA/fMLP-induced EET/DHET synthesis and vasoconstriction but not oedema formation, suggesting a major contribution of LTs/PTs to vascular leakage and of EETs/DHETs to pressor response.

Consequently, generation of EETs/DHETs is greater than that of LTs plus HETEs and PTs in ex vivo perfused human lungs upon microbial challenge suggesting a substantial contribution of these mediators to inflammatory-infectious pulmonary injury.

Harvard Citation style: Kiss, L., Schuette, H., Padberg, W., Weissmann, N., Mayer, K., Gessler, T., et al. (2010) Epoxyeicosatrienoates are the dominant eicosanoids in human lungs upon microbial challenge, European Respiratory Journal, 36(5), pp. 1088-1098. https://doi.org/10.1183/09031936.00000309

APA Citation style: Kiss, L., Schuette, H., Padberg, W., Weissmann, N., Mayer, K., Gessler, T., Voswinckel, R., Seeger, W., & Grimminger, F. (2010). Epoxyeicosatrienoates are the dominant eicosanoids in human lungs upon microbial challenge. European Respiratory Journal. 36(5), 1088-1098. https://doi.org/10.1183/09031936.00000309