Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae

Cytokine expression of cord and adult blood mononuclear cells in response to Streptococcus agalactiae
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DOI:
10.1203/00006450-200203000-00007
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发表时间:
2002-03-01
期刊:
影响因子:
3.6
通讯作者:
Brandis, M
Brandis, M
中科院分区:
医学3区
文献类型:
--
作者:
Berner, R;Welter, P;Brandis, M

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新生儿细菌性脓毒症通常以暴发性临床病程和血浆促炎细胞因子水平高为特征。为了评估特异性感染刺激对新生儿免疫系统的体外激活作用,我们检测了健康新生儿脐带血细胞对无乳链球菌(GBS)、脂多糖(LPS)和脂质胆酸(LTA)的肿瘤坏死因子- α (tnf - α)、il -1 β、IL-6和IL-8的表达。比较脐带血和成人外周血单核细胞中细胞因子的表达。热杀GBS刺激后脐带血细胞培养上清中tnf - α和IL-6水平(10(7)/mL)显著高于LPS(2杯/mL)或LTA(2杯/mL) (tnf - α: 2215 vs 267.5 vs 40 pg/mL, p = 0.001; IL-6: 9667 vs 4909 vs 919 pg/mL, p = 0.006)。在不同时间用GBS、LPS或LTA刺激脐带或成人血细胞后,tnf - α、il -1 β、IL-6和IL-8的mRNA表达同样明显。针对单核细胞受体分子CD14的单抗并未抑制GBS刺激后脐带血单核细胞中细胞因子的释放。总之,在促炎细胞因子的表达方面,感染刺激激活脐带血细胞与成人免疫反应相当。与LPS和LTA相比,GBS尤其被证明是新生儿免疫系统的有效激活剂。CD14似乎不是GBS激活脐带血细胞的关键分子。
Neonatal bacterial sepsis is often characterized by a fulminant clinical course and highly elevated plasma levels of proinflammatory cytokines. To evaluate in vitro activation of the neonatal immune system by specific infectious stimuli, cord blood cells from healthy neonates were examined for expression of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, and IL-8 in response to Streptococcus agalactiae (GBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). Cytokine-expression was compared in mononuclear cells from cord and adult peripheral blood. TNF-alpha and IL-6 levels in the supernatant of cord blood cell cultures were significantly higher after stimulation with heat-killed GBS (10(7)/mL) than with LPS (2 mug/mL) or LTA (2 mug/mL) (TNF-alpha: 2215 versus 267.5 versus 40 pg/mL, p = 0.001; IL-6: 9667 versus 4909 versus 919 pg/mL, p = 0.006). mRNA expression of TNF-alpha, IL-1beta, IL-6, and IL-8 was equally pronounced after stimulation with either GBS, LPS, or LTA in cord or adult blood cells at various times. A MAb directed against the monocyte receptor molecule CD14 did not inhibit the release of cytokines in cord blood mononuclear cells after stimulation with GBS. In summary, activation of cord blood cells by infectious stimuli is comparable to the adult immune response in terms of expression of proinflammatory cytokines. GBS in particular proves to be a potent activator of the neonatal immune system when compared with LPS and LTA. CD14 seems not to be a crucial molecule for activation of cord blood cells by GBS.