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Platelet activating factor and tracheobronchial respiratory glycoconjugate release in feline and human explants: Involvement of the lipoxygenase pathway

  • Inflammation and Immunomodulation
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Abstract

It has been suggested that platelet activating factor (PAF) may participate in many aspects of bronchial asthma, including stimulation of mucus secretion. Feline tracheal and human bronchial explant production of respiratory glycoconjugates (RGC) in response to platelet activating factor (PAF) was investigatet, in order to differentiate the actions of this putative mediator on mucus secretion. PAF caused a dose-dependent increase in RGC release in concentrations ranging from 100–0.5 μM during a 1–2 hours incubation with either feline or human explants, and the effect was inhibited by the PAF receptor antagonists Ro 19-3704. Several lines of evidence suggest that PAF enhances RGC release indirectly through stimulation of the production of lipoxygenase metabolites of arachidonic acid. 1) Incubation of 10 μM PAF together with arachidonic acid (100 μg/ml) enhances PAF's stimulatory effect on RGC release in cats. 2) The cyclooxygenase inhibitor ibuprofen (65 and 420 μM) either failed to effect or slightly enhanced PAF induced RGC release in both species. 3) The combined cyclooxygenase and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) as well as the putatively specific 5-lipoxygenase inhibitor L-651, 392 (both at 50 μM) inhibited the response to PAF in both species. 4) The putative LTD4 receptor antagonists (L-660, 711, 100 μM) slightly reduced the PAF secretory response in human bronchi. We conclude that PAF causes specific receptor mediated RGC release. This response is indirectly mediated through the generation of lipoxygenase metabolite formation including 5-lipoxygenase pathway metabolites.

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Authors and Affiliations

  1. Gritical Care Medicine Department, Clinical Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

    J. D. Lundgren, C. Logun & J. H. Shelhamer

  2. Allergic Disease Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

    M. Kaliner

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  1. J. D. Lundgren
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  2. M. Kaliner
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  3. C. Logun
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  4. J. H. Shelhamer
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Additional information

Parts of this report has previously been published as abstract in: Clin. Res., 36(3), A257 (1988); J. Allergy Clin. Immunol., 83, 274 (1989); and FASEB J., 3(3), A609 (1989).

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Lundgren, J.D., Kaliner, M., Logun, C. et al. Platelet activating factor and tracheobronchial respiratory glycoconjugate release in feline and human explants: Involvement of the lipoxygenase pathway. Agents and Actions 30, 329–337 (1990). https://doi.org/10.1007/BF01966296

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  • DOI: https://doi.org/10.1007/BF01966296

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