Metabolism of platelet-activating factor in isolated perfused rat lung.

Haroldsen, Peter E.; Voelkel, Norbert F.; Henson, Jan E.; Henson, Peter M.; Murphy, Robert C.

doi:10.1172/jci113028

Cited by 30 publications

(4 citation statements)

References 29 publications

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“…The exocrine cells in the airways are thought to secrete a surface 'blanket' of mucus for lubricating the airways to protect against noxious airborne particles (Weibel, 1985). The Clara cells in many species have been described in association with functional aspects such as the synthesis, storage and secretion of bioactive substances including proteins (Massaro, 1989;Plopper et aI., 1991), pulmonary surfactant apoproteins (Phelps & Floros, 1988;Massaro, 1989;Plopper et al, 1991) or protein (Singh & Katyal, 1984;Bedetti et al, 1987), antileukoproteases (Willems et al, 1989), arachidonic acid metabolities (Haroldsen et al, 1987) and xenobiotic metabolites (Massaro, 1989). So far, however, no opioid peptide has been reported to be present in the serous and Clara cells in either immature or adult mammals.…”

Section: Discussionmentioning

confidence: 99%

Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system

et al. 1994

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The localization of [D-Ala2]deltorphin I, a delta-opioid receptor ligand, was studied in the lower respiratory tract of developing rats using an immunohistochemical method. [D-Ala2]-like immunoreactive cells were detected first in the principal bronchus as early as embryonic day 16. As embryos grew, positive cells became gradually visible everywhere from principal bronchi to respiratory bronchioles. The density of positive cells reached the highest level on embryonic day 21, but decreased gradually after birth. Positive cells were no longer seen on postnatal day 30 in any region of the airways. No positive cells were ever found in the trachea or alveoli of rats at any age studied. Ultrastructural examination indicated that the immunoreactive cells possessed a similar morphology to serous or Clara cells of the respiratory epithelium. Immunoreaction products tended to locate at the apical cytoplasm of positive cells. The results suggests that [D-Ala2]-like molecule(s) may be expressed transiently in serous cells or Clara cells, or both, of the rat bronchopulmonary tract. Such a molecule may act as a pulmonary growth-promoting or a differentiation-initiating factor in an early period of lung development.

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Section: Discussionmentioning

confidence: 99%

Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system

et al. 1994

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“…One possible reason for this discrepancy is the great avidity of the type II pneumocytes for PAF, 95% of the radiolabelled PAF instilled into the rat lung airways being selectively retained by these cells. 43 Since this effect is not antagonize d by BN 52021 and the high lipid content of the se cells, it is possible that PAF-type II pneumocyte interaction is not mediated by receptors.…”

Section: Discussionmentioning

confidence: 99%

BN 52021 (a platelet activating factor‐receptor antagonist) decreases alveolar macrophage‐mediated lung injury in experimental extrinsic allergic alveolitis

Pérez-Arellano

Martin

López-Novoa

et al. 1998

Mediators of Inflammation

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Several lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA). The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs. Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue. In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by measuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF) lactic hydrogenase activity and BALF alkaline phosphatase activity) and parameters of systemic response to the challenge (acute phase reagents). We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (beta-glucuronidase and tartrate-sensitive acid phosphatase) to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF.

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“…Autoradiographic analysis of the cellular distribution of the [3H]PAF metabolites in the lung tissue indicated labeling of two cell types, the alveolar type II cell and the nonciliated bronchiolar epithelial cell (Clara cell) [23]. PAF was rapidly metabolized (90% in 10 min) by alveolar type II cells [24].…”

Section: Discussionmentioning

confidence: 99%

Decrease of ciliary beat frequency by platelet activating factor: Protective effect of ketotifen

Kahhak

Roche²,

Dubray³

et al. 1996

Inflamm Res

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The ciliary beat frequency (CBF) of the tracheal epithelial cells controls in part the respiratory tract mucociliary transport efficiency. We investigated the effects on CBF of PAF-acether (PAF) and its metabolite/precursor lyso-PAF. Guinea-pig tracheal rings were incubated for 3 to 6h with 1 microM PAF (C16, C18, C16/C18: 80/20%), lyso-PAF C16 or lyso-phosphatidylcholine (LPC). CBF changes were assessed by microphotooscillography (mean number of measures per ring = 14). We also examined the effect on PAF-induced CBF changes of the PAF receptor-antagonist WEB 2086, the anti-asthmatic/anti-anaphylactic drug ketotifen and the anti-histamine H1 pyribenzamine. CBF of control rings exposed to vehicle only from 0 to 6h showed no significant statistical variations (hertz, mean +/- SEM): 10.8 +/- 0.1 (n of measures = 890). By contrast, 1 microM C16, C18, and C16/C18 PAF significantly inhibited CBF after 3 to 6h incubation. C16 and C16/C18 PAF were more potent than C18 PAF (8.8 +/- 0.2, n = 112, 8.7 +/- 0.2, n = 64, and 9.6 +/- 0.1, n = 537 respectively; ANOVA analysis, p < 0.001 from control). At the same concentration, lyso-PAF also inhibited CBF, 9.5 +/- 0.1 (n = 197, p < 0.001) but not LPC, 10.5 +/- 0.2 (n = 127). WEB 2086 inhibited lyso-PAF and C16/18 PAF-induced CBF decrease. Preincubation (20 min) with ketotifen but not with pyribenzamine (1 microM) also suppressed the CBF inhibitory effect of PAF and lyso-PAF. Incubation of [3H]PAF with tracheal rings from 10 min to 6h resulted in its partial metabolism (25%) into [3H]lyso-PAF and a compound with a short retention time (10 min). [3H]lyso-PAF incubated for 3h with tracheal rings was partially metabolized (10%) into [3H]PAF and a compound with a short retention time. The PAF-induced decrease of CBF is congruent with its influence on pulmonary clearance, possibly via a specific receptor, since WEB 2086 abolished the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen may contribute to the therapeutic properties of this antiallergic drug.

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Metabolism of platelet-activating factor in isolated perfused rat lung.

Cited by 30 publications

References 29 publications

Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system

Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system

BN 52021 (a platelet activating factor‐receptor antagonist) decreases alveolar macrophage‐mediated lung injury in experimental extrinsic allergic alveolitis

Decrease of ciliary beat frequency by platelet activating factor: Protective effect of ketotifen

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