Wahle Matthias, Greulich Timm, Baerwald Christoph G O, Häntzschel Holm, Kaufmann Andreas
Department of Medicine IV, University Hospital Leipzig, Liebigstrasse 22, 04103 Leipzig, Germany.
Immunobiology. 2005;210(1):43-52. doi: 10.1016/j.imbio.2005.02.004.
The impact of catecholamines on cytokine production and expression of adhesion molecules by human neutrophils was evaluated in vitro. Neutrophils were separated from venous blood of healthy subjects. The generation of intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ was determined after incubation with catecholamines. Resting and lipopolysaccharide (LPS)-activated neutrophils were tested for synthesis of interleukins (IL-6, IL-8) and tumor necrosis factor alpha (TNF-alpha). In addition, the expression of the adhesion molecules CD15, CD44, and CD54 was evaluated in resting and activated neutrophils. Increasing concentrations (1 nM-1 mM) of epinephrine (EPI) were used to study the influence of activation of beta2-adrenergic receptors (beta2R) on cytokine production and adhesion molecule expression. Incubation with catecholamines induced an increase in cAMP but not Ca2+ in neutrophils. Only IL-8 was detected following stimulation with LPS and was unchanged upon co-incubation with EPI. The expression of CD15 and CD44 decreased spontaneously in vitro. The density of CD44 increased in the presence of very high doses of EPI (1 mM). Expression of CD54 on resting neutrophils increased upon activation. The density of CD54 on activated neutrophils was reduced upon co-incubation with 1 mM EPI for 6 h. However, 1 mM EPI for 12 and 18 h decreased the spontaneous loss of CD54 on resting neutrophils. Beta2R are functionally coupled to signalling cascades in human neutrophils. Nevertheless, the impact of catecholamines on IL-8 synthesis and expression of CD15, CD44, and CD54 is limited.
在体外评估了儿茶酚胺对人中性粒细胞细胞因子产生及黏附分子表达的影响。从健康受试者的静脉血中分离出中性粒细胞。与儿茶酚胺孵育后，测定细胞内环磷酸腺苷（cAMP）和钙离子（Ca2+）的生成。检测静息和脂多糖（LPS）激活的中性粒细胞中白细胞介素（IL-6、IL-8）和肿瘤坏死因子α（TNF-α）的合成情况。此外，还评估了静息和激活的中性粒细胞中黏附分子CD15、CD44和CD54的表达。使用递增浓度（1 nM - 1 mM）的肾上腺素（EPI）来研究β2-肾上腺素能受体（β2R）激活对细胞因子产生和黏附分子表达的影响。儿茶酚胺孵育可诱导中性粒细胞中cAMP增加，但Ca2+无变化。LPS刺激后仅检测到IL-8，与EPI共同孵育后其水平未改变。CD15和CD44的表达在体外自发降低。在极高剂量EPI（1 mM）存在时，CD44的密度增加。静息中性粒细胞激活后CD54的表达增加。与1 mM EPI共同孵育6小时后，激活的中性粒细胞上CD54的密度降低。然而，1 mM EPI作用12小时和18小时可减少静息中性粒细胞上CD54的自发丢失。β2R在功能上与人中性粒细胞中的信号级联相关。尽管如此，儿茶酚胺对IL-8合成及CD15、CD44和CD54表达的影响有限。
