The effects of glucocorticoids and agents affecting membrane phospholipid metabolism on $ beta$-adrenergic receptors ($ beta$AR) have been studied in A549 cultured human lung tumor cells and in IM-9 cultured human lymphocytes. Various glucocorticoids increased the density of $ beta$AR in A549 lung cells but not in IM-9 lymphocytes, although they did increase insulin receptor density in IM-9 lymphocytes. In contrast, bee venom phospholipase A$ sb2$ (0.05-0.2 units/ml), but not phospholipases C or D., downregulated $ beta$AR in IM-9 lymphocytes, but did not affect $ beta$AR in A549 lung cells. Upregulation of $ beta$AR by glucocorticoids was partially reversed by arachidonic acid (10 $ mu$M) but not by lysophospatidylcholine. These results suggest that glucocorticoids upregulate pulmonary $ beta$AR partly through their inhibition of membrane phospholipase A2 and the subsequent generation of arachidonic acid and/or its metabolites, which may act by modulating a direct effect of glucocorticoids on the synthesis of $ beta$AR. Coculturing IM-9 lymphocytes and A549 lung cells results in a 2-3-fold increase in the density of $ beta$AR in A549 lung cells. Lymphocyte conditioned medium (LCM) has the same effect, which is moderately sensitive to heat, is retained by ultrafiltration over a 10,000 m.w. cut-off filter, and is reduced by trypsin treatment or by preincubation of lymphocytes with cycloheximide (1$ mu$m). Treatment of lung cells with cycloheximide also prevents the effect of LCM. Glucocorticoids, which also increase $ beta$AR density in A549 lung cells, markedly potentiate the effects of LCM. Gel permeation HPLC of LCM yields 3 peaks of biological activity with M.W. 70,000, 35,000 and 15,000. Monocytic Interleukin-1 (IL-1) mimics the effect of LCM in that it increases $ beta$AR density in A549 lung cells and its effect is potentiated by cortisol. Recombinant IL-1$ alpha$ is somewhat more potent then IL-1$ beta$, while Interleukin-2 and interferon-$ alpha$ are inef
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74250 |
| Date | January 1989 |
| Creators | Stern, Ligia R. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000937339, proquestno: AAINL57333, Theses scanned by UMI/ProQuest. |
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