help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grimminger, F.
Right arrow Articles by Seeger, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grimminger, F.
Right arrow Articles by Seeger, W.

Am. J. Respir. Cell Mol. Biol., Vol 16, No. 3, Mar 1997, 317-324.

Synthesis of 4- and 5-series leukotrienes in the lung microvasculature challenged with Escherichia coli hemolysin: critical dependence on exogenous free fatty acid supply

F Grimminger, K Mayer, L Kiss, H Wahn, D Walmrath and W Seeger
Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.

Escherichia coli hemolysin (HlyA) has been identified as a potent inductor of phosphoinositide hydrolysis and related metabolic responses in neutrophils (Grimminger and colleagues, 1991, J. Clin. Invest. 88:1531-1539). In isolated perfused rabbit lungs, which harbor a large number of entrapped microvascular leukocytes, we investigated the effect of a low dose of HlyA on lipoxygenase product formation in the presence of exogenous free arachidonic acid (AA), eicosapentaenoic acid (EPA), or both precursor fatty acids. Leukotrienes (LT) and hydroxyeicosatetra(penta)enoic acids (HET[P]E) in the recirculating perfusate were quantified using high-performance liquid chromatography techniques. In the absence of exogenous precursor fatty acid supply, 0.02 hemolytic units/ml HlyA elicited only minor amounts of LTs and 5- HETE. AA, 10 microM, provoked the generation of limited quantities of LTB4, LTE4, and 5-HETE. Combined application of HlyA and AA caused a manifold amplification of 4-series LT and 5-HETE generation, with predominance of cysteinyl-LTs. EPA, 10 microM, elicited the synthesis of 5-series LTs accompanied by marked quantities of 5-HEPE. Dual stimulation with HlyA and EPA provoked exclusive generation of excessive quantities of all 5-series 5-lipoxygenase products. When HlyA was administered in the presence of both AA (10 microM) and EPA (10 microM), the n-3 fatty acid clearly turned out to be the preferred substrate, with ratios of the various 5-series to 4-series products ranging between 1.8 and 14.5. Moreover, the absolute quantities of AA- derived metabolites and the total sum of all 5-lipoxygenase products was markedly reduced under these conditions. We conclude that the HlyA- evoked 5-lipoxygenase product formation in the pulmonary vasculature of the rabbit is critically dependent on the presence of free precursor fatty acids. The profile of LTs suggests neutrophil (PMN)-related transcellular eicosanoid synthesis as a major underlying metabolic pathway. EPA represents the preferred substrate as compared with AA, resulting in a marked suppression of AA metabolite formation. Therapeutic attempts to provide n-3 fatty acids via the intravenous route may have a major impact on lipid mediator profiles in PMN-related inflammatory events.


This article has been cited by other articles:


Home page
 EndocrinologyHome page
Y.-M. Mu, T. Yanase, Y. Nishi, A. Tanaka, M. Saito, C.-H. Jin, C. Mukasa, T. Okabe, M. Nomura, K. Goto, et al.
Saturated FFAs, Palmitic Acid and Stearic Acid, Induce Apoptosis in Human Granulosa Cells
Endocrinology, August 1, 2001; 142(8): 3590 - 3597.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
F. Rose, L. Kiss, F. Grimminger, K. Mayer, U. Grandel, W. Seeger, E. Bieniek, and U. Sibelius
E. coli hemolysin-induced lipid mediator metabolism in alveolar macrophages: impact of eicosapentaenoic acid
Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L100 - L109.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. KISS, H. SCHÜTTE, K. MAYER, H. GRIMM, W. PADBERG, W. SEEGER, and F. GRIMMINGER
Synthesis of Arachidonic Acid-Derived Lipoxygenase and Cytochrome P450 Products in the Intact Human Lung Vasculature
Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1917 - 1923.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
F. Grimminger, K. Mayer, L. Kiss, D. Walmrath, and W. Seeger
PAF-induced synthesis of tetraenoic and pentaenoic leukotrienes in the isolated rabbit lung
Am J Physiol Lung Cell Mol Physiol, February 1, 2000; 278(2): L268 - L275.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1997 American Thoracic Society.