title: Adrenal hormone deprivation affects macrophage catecholamine metabolism and β2-adrenoceptor density, but not propranolol stimulation of tumour necrosis factor-α production.
abstract: Catecholamines modulate the production of inflammatory mediators by macrophages in an autocrine/paracrine manner. They also tune β2-adrenoceptor expression. Glucocorticoids influence catecholamine metabolism and adrenoceptor expression in many cell types. We hypothesized that adrenal hormones affect the production of tumour necrosis factor-α (TNF-α) and NO by macrophages by altering the modulatory influence of catecholamines. To prove the hypothesis, peritoneal exudate macrophages from propranolol-treated non-operated and adrenalectomized rats and from corticosterone-supplemented adrenalectomized rats were examined for lipopolysaccharide-stimulated NO and TNF-α production in vitro and for expression of β2-adrenoceptors and major catecholamine-metabolizing enzymes. Glucocorticoid deprivation increased NO production by macrophages, whereas 4 days of propranolol treatment was ineffective in this respect. However, propranolol treatment, via β2-adrenoceptor blockade, increased production of TNF-α by macrophages in both non-operated and adrenalectomized rats (showing dramatically enhanced TNF-α production due to a lack of circulating glucocorticoids) for the same value. The expression of β2-adrenoceptor was increased in peritoneal macrophages that were freshly isolated from non-operated, propranolol-treated and adrenalectomized rats (due to adrenal catecholamine deficiency). Propranolol did not affect macrophage β2-adrenoceptor expression in adrenalectomized rats. Given that propranolol increased the density of macrophage tyrosine hydroxylase expression only in non-operated rats and affected the mRNA expression of monoamine oxidase-A in neither non-operated nor adrenalectomized animals, a significant influence of propranolol on peritoneal exudate cell noradrenaline content was found only in non-operated rats. A lack of circulating adrenal hormones also affected noradrenaline metabolism and content in peritoneal exudate cells including macrophages. Collectively, despite differences in the abundance of macrophage catecholamine-β2-adrenoceptor system components and in the TNF-α response to lipopolysaccharide between adrenalectomized and non-operated rats, propranolol increased TNF-α production by the same amount in macrophages from these two groups of animals.
authors.affiliation: Immunology Research Center 'Branislav Janković', Vojvode Stepe 458, 11221 Belgrade, Serbia. sstanojevic@torlakinstitut.com
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stanojevic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Dimitrijevic
authors.forename: Natasa
authors.initials: N
authors.lastname: Kustrimovic
authors.forename: Katarina
authors.initials: K
authors.lastname: Mitic
authors.forename: Vesna
authors.initials: V
authors.lastname: Vujic
authors.forename: Gordana
authors.initials: G
authors.lastname: Leposavic
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011433:Propranolol; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D003345:Corticosterone; D009638:Norepinephrine