Schopf R E, Lemmel E M
J Immunopharmacol. 1983;5(3):203-16. doi: 10.3109/08923978309039106.
The control by beta-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (M phi) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN and M phi exhibit differential sensitivity to beta-adrenergic stimulation. For beta-adrenergic stimulation we applied fenoterol ranging from 10(-5) to 10(-9) M x 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10(-6) M both for PMN and M phi. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the beta-adrenergic antagonist propranolol at 10(-6) and 10(-7) M the suppression effect of fenoterol could be reversed in dose-dependency. Preincubation with fenoterol revealed that the inhibitory action on M phi persisted, in contrast, no such suppression could be verified with PMN. Our findings indicate the control of the production of oxygen intermediates of human PMN and M phi by beta-adrenergic stimulation. Furthermore, selective functional modulation of resting PMN and M phi by beta-adrenoceptors is suggested. These effects may be of importance in vivo, in particular since fenoterol was applied in pharmacological doses.
采用化学发光法在体外研究了β-肾上腺素能受体对酵母聚糖刺激的人多形核白细胞(PMN)和单核细胞(M phi)产生氧自由基的控制作用。此外,我们还研究了PMN和M phi对β-肾上腺素能刺激是否表现出不同的敏感性。对于β-肾上腺素能刺激,我们应用了浓度范围为10^(-5)至10^(-9) M×2.7的非诺特罗。我们发现氧自由基的产生呈剂量依赖性抑制,PMN和M phi的半数抑制浓度(ID50)均约为10^(-6) M。通过评估乳酸脱氢酶释放,可排除该药物的细胞毒性作用。当与10^(-6)和10^(-7) M的β-肾上腺素能拮抗剂普萘洛尔一起孵育时,非诺特罗的抑制作用可呈剂量依赖性逆转。用非诺特罗预孵育显示,对M phi的抑制作用持续存在,相比之下,PMN未证实有这种抑制作用。我们的研究结果表明,β-肾上腺素能刺激可控制人PMN和M phi的氧中间体产生。此外,提示β-肾上腺素能受体对静息PMN和M phi有选择性功能调节作用。这些作用在体内可能很重要,特别是因为非诺特罗是以药理剂量应用的。