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J. Biol. Chem., Vol. 263, Issue 31, 15876-15879, 11, 1988
L Stern and G Kunos
Coculturing IM9 human lymphocytes and A549 human lung adenocarcinoma cells
results in a 2-3-fold increase in the density of beta-adrenergic receptors
in the latter, as quantified by 125I-cyanopindolol binding.
Lymphocyte-conditioned medium (LCM) has the same effect, which is
moderately sensitive to heat, is retained by ultrafiltration over a Mr
10,000 cut-off filter, and is reduced by trypsin treatment or by
preincubation of lymphocytes with 0.3 micrograms/ml cycloheximide.
Treatment of lung cells with cycloheximide also prevents the effect of LCM.
Glucocorticoids, which also increase beta-receptor density in A549 cells,
markedly potentiate the effect of LCM. Gel permeation high pressure liquid
chromatography of LCM yields three peaks of biological activity with Mr
70,000, 35,000, and 15,000. Monocytic interleukin-1 (IL-1) mimics the
effect of LCM in that it increases beta-receptor density in A549 cells
(EC50 0.3 pM), and its effect is potentiated by cortisol. Recombinant IL-1
alpha is somewhat more potent than IL-1 beta, while interleukin-2 and
interferon-alpha are ineffective. Tumor necrosis factor alpha causes a
small increase in beta-receptors, which is not influenced by
glucocorticoids. A polyclonal anti-IL-1 antibody inhibits the effect of
IL-1 and the effect of the 15-kDa but not the 35- and 70-kDa fractions of
LCM. The activity of the latter two fractions is also unaffected by
anti-tumor necrosis factor alpha antibody. These results indicate that
lymphocytes release protein factors including IL- 1 that up-regulate
pulmonary beta-adrenergic receptors by an action that involves protein
synthesis. The possible relevance of this regulatory mechanism for the
pathomechanism of certain respiratory diseases is discussed.
Synergistic regulation of pulmonary beta-adrenergic receptors by glucocorticoids and interleukin-1
Department of Pharmacology and Medicine, McGill University, Montreal, Canada.
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