Effects of leukotrienes C4 and D4 on glycoprotein and lysozyme secretion by human bronchial mucosa

doi:10.1016/0090-6980(83)90101-6

Prostaglandins

Volume 25, Issue 2, February 1983, Pages 155-170

Prostaglandins

https://doi.org/10.1016/0090-6980(83)90101-6 Get rights and content

Abstract

The effects of leukotrienes C₄ (LTC₄) and D₄ (LTD₄) on the secretion by human bronchial mucosa of [¹⁴C]glucosamine-labeled, trichloro-acetic acid/phosphotungstic acid-precipitable glycoprotein and lysozyme were evaluated $in vitro$ . LTC₄ and LTD₄, in the concentration range of 0.16 to 1600 nM, induced a dose-related increase in the release of radiolabeled glycoprotein, but not of lysozyme. This secretagogue effect was selective for high molecular weight glycoproteins of about 2–5 × 10⁶ daltons, and the median effective concentrations (EC₅₀ of LTC₄ of 9.4 × 10⁻⁹ M and of LTD₄ of 2.44 × 10⁻⁸ M, indicate that these leukotrienes are approximately 100-fold more potent than the cholinergic agonist methacholine. Incubation of [¹⁴C]glucosamine-labeled bronchial mucosal explants with LTC₄ or LTD₄ for six sequential 15-min periods revealed a rapid, progressive decrement in glycoprotein release, compatible with stimulatory action on secretion rather than augmentation of the rate of glycoprotein synthesis. This interpretation is also consistent with the finding that the specific activity (ratio of bound radiolabel: protein content) of the macromolecular glycoprotein secreted by the explants is not changed with stimulation of release by the leukotrienes. Based upon the activity of synthetic leukotriene analogs, the specific C-6 chirality of the sulfidopeptide of LTD₄, the presence of a hydroxyl at C-5 and the presence of eiconsanoid carbons 9–20 were no importance for secretagogue activity. These findings contrast with the stereochemical requirements for the spasmogenic response to sulfidopeptide leukotrienes and suggest that leukotriene-induced secretion is not likely to be mediated via a specific receptor.

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Effects of leukotrienes C4 and D4 on glycoprotein and lysozyme secretion by human bronchial mucosa

Abstract

Tetrahedron Lett.

Tetrahedron Lett.

Exp. Mol. Pathol.

Chest

J. Biol. Chem.

Immunologic and neuropharmacologic stimulation of mucous glycoprotein release from human airways in vitro

J. Clin. Invest.

Effects of arachidonic acid, monohydroxyeicosatetraenoic acid nad prostaglandins on the relese of mucous glycoprotein from human airways in vitro

J. Clin. Invest.

Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources

The effects of arachinoids and leukotrienes on the release of mucus from human airways

Chest

Inhibition of glycoconjugate secretion by colchicine and cytochalasin B. An in vitro study of human airway

Cell Tissue Res.

Ultrastructural immunocytochemical localization of lysozyme in human bronchial glands

Thorax

Inhibition by vasoactive intestinal peptide of glycoconjugate and lysozyme secretion by human airways in vitro

Am. Rev. Respir. Dis.

Effects of leukotrienes C₄ and D₄ on glycoprotein and lysozyme secretion by human bronchial mucosa

Immunologic and neuropharmacologic stimulation of mucous glycoprotein release from human airways $in vitro$

Effects of arachidonic acid, monohydroxyeicosatetraenoic acid nad prostaglandins on the relese of mucous glycoprotein from human airways $in vitro$

Inhibition of glycoconjugate secretion by colchicine and cytochalasin B. An $in vitro$ study of human airway

Inhibition by vasoactive intestinal peptide of glycoconjugate and lysozyme secretion by human airways $in vitro$