Victoni Tatiana, Salvator Hélène, Abrial Charlotte, Brollo Marion, Porto Luis Cristovão Sobrino, Lagente Vincent, Naline Emmanuel, Grassin-Delyle Stanislas, Devillier Philippe
Laboratory of Histocompatibility and Cryopresevation, Laboratory of Tissue Repair, Rio de Janeiro, Brazil.
Laboratory of Research in Respiratory Pharmacology-UPRES EA220, UFR Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin, Université Paris-Saclay, 11, rue Guillaume Lenoir, F-92150, Suresnes, France.
Respir Res. 2017 Jun 21;18(1):126. doi: 10.1186/s12931-017-0613-y.
β-adrenoceptor agonists have been shown to reduce the lipopolysaccharide (LPS)-induced cytokine release by human monocyte-derived macrophages (MDMs). We compare the expression of β-adrenoceptors and the inhibitory effect of formoterol and salmeterol on the LPS-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and a range of chemokines (CCL2, 3, 4, and IL-8) by human lung macrophages (LMs) and MDMs.
LMs were isolated from patients undergoing resection and MDMs were obtained from blood monocytes in the presence of GM-CSF. LMs and MDMs were incubated in the absence or presence of formoterol or salmeterol prior to stimulation with LPS. The effects of formoterol were also assessed in the presence of the phosphodiesterase inhibitor roflumilast.
LPS-induced cytokine production was higher in LMs than in MDMs. Salmeterol and formoterol exerted an inhibitory effect on the LPS-induced production of TNF-α, IL-6, CCL2, CCL3, and CCL4 in MDMs. In contrast, the β-adrenoceptor agonists were devoid of any effect on LMs - even in the presence of roflumilast. The expression of β-adrenergic receptors was detected on Western blots in MDMs but not in LMs.
Concentrations of β-adrenoceptor agonists that cause relaxation of the human bronchus can inhibit cytokine production by LPS-stimulated MDMs but not by LMs.
β-肾上腺素能受体激动剂已被证明可减少脂多糖（LPS）诱导的人单核细胞衍生巨噬细胞（MDM）释放细胞因子。我们比较了人肺巨噬细胞（LM）和MDM中β-肾上腺素能受体的表达，以及福莫特罗和沙美特罗对LPS诱导的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和一系列趋化因子（CCL2、3、4和IL-8）释放的抑制作用。
从接受切除术的患者中分离出LM，在粒细胞-巨噬细胞集落刺激因子（GM-CSF）存在的情况下从血液单核细胞中获得MDM。在LPS刺激之前，将LM和MDM在不存在或存在福莫特罗或沙美特罗的情况下孵育。还在磷酸二酯酶抑制剂罗氟司特存在的情况下评估了福莫特罗的作用。
LPS诱导的细胞因子产生在LM中高于MDM。沙美特罗和福莫特罗对LPS诱导的MDM中TNF-α、IL-6、CCL2、CCL3和CCL4的产生具有抑制作用。相比之下，β-肾上腺素能受体激动剂对LM没有任何作用——即使在罗氟司特存在的情况下也是如此。在MDM的蛋白质免疫印迹中检测到β-肾上腺素能受体的表达，但在LM中未检测到。
可使人支气管舒张的β-肾上腺素能受体激动剂浓度可抑制LPS刺激的MDM产生细胞因子，但不能抑制LM产生细胞因子。
