您的位置: 首页 > 2015年9月 第46卷 第5期 > 文字全文
2023年7月 第38卷 第7期11
目录

磷酸二酯酶4抑制剂对人巨噬细胞噬菌能力的影响

The influence of phosphodiesterases 4 inhibitor on the phagocytosis of bacteria by human macrophage

来源期刊: 广州医药 | 5-8 发布时间:2021-11-30 收稿时间:2025/11/13 16:40:35 阅读量:7
作者:
关键词:
磷酸二酯酶4抑制剂咯利普兰巨噬细胞金黄色葡萄球菌流感嗜血杆菌
Phosphodiesterases 4 inhibitorRolipramMacrophageHeamophilus influenzaeStaphylococcus aureus
DOI:
10.3969/j.issn.1000-8535.2015.05.002
收稿时间:
2015-03-15 
修订日期:
 
接收日期:
 
引用总数:
0  
目的 探讨磷酸二酯酶4抑制剂对人肺泡巨噬细胞(AM)吞噬非生物性颗粒及革兰阳性菌、阴性菌能力的影响。方法 使用Ficolll-Hypaque密度梯度法将外周血单核细胞分离的静脉血,在含有2 ng/m GM-CSF的培养液中经12天诱导培养成AM替代细胞模型—单核细胞源性巨噬细胞(MDM)。用酶标仪检测MDM经磷酸二酯酶4抑制剂Rolipram预处理过夜(16~18 h)后吞噬荧光标记的非生物颗粒Beads和热灭活的流感嗜血杆菌(H.influenzae)、金黄色葡萄球菌(S.aureus)量的改变,另使用MTT法检测细胞活性。结果 成功建立的MDM细胞模型对Beads和细菌的吞噬呈时效关。Rolipram在实验浓度(10~8~10-5 M)下对MDM吞噬Beads、H.influenzae和S.aureus能力无明显促进或抑制作用,也不影响MDM的活性。结论 磷酸二酯酶4抑制剂不会因升高巨噬细胞内cAMP水平而影响其吞噬非生物颗粒和细菌的能力。
Objective To investigate the influence of phosphodiesterases 4 inhibitor on the phagocytosis of non-biological particles and gram-positive bacteria, gram-negative bacteria by human alveolar macrophages. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood from 12 healthy volunteers using Ficoll-Hypaque density gradients. Monocytes were incubated with media containing 2 ng/ml GM-CSF for 12d to allow full differentiation into macrophage (MDM), a functionally equivalent model of human AM. MDM were pretreated with Rolipram overnight (16-18h),phagocytosis of fluorescent labeled beads and H.influenzae,S.aureus by MDM was measured using a fluostar optima fluorimeter. Cell viability was assay with MTT. Results MDM phagocytosis of beads and bacteria was a time-dependant process. Rolipram in the concentration of 10-8-10-5M didn't inhibit or promote phagocytosis of beads and bacteria by MDM, and didn't affect the cell viability. Conclusion Phosphodiesterases 4 inhibitor would not affect the human macrophage phagocytic capacity of non-biological particles and bacteria associated with enhanced intracellular cAMP level.
1、 Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease[J]. N Engl J Med,2008,359(22):2355-2365. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease[J]. N Engl J Med,2008,359(22):2355-2365.
2、 Wood LG, Simpson JL, Hansbro PM, et al. Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia[J]. Free Radic Res,2010,44(2):146-154. Wood LG, Simpson JL, Hansbro PM, et al. Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia[J]. Free Radic Res,2010,44(2):146-154.
3、 Zhang Q, Illing R, Hui CK, et al. Bacteria in sputum of stable severe asthma and increased airway wall thickness[J]. Respir Res,2012(13):35-45. Zhang Q, Illing R, Hui CK, et al. Bacteria in sputum of stable severe asthma and increased airway wall thickness[J]. Respir Res,2012(13):35-45.
4、 Donnelly LE, Tudhope SJ, Fenwick PS, et al. Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages[J]. Eur Respir J,2010,36(1):178-186. Donnelly LE, Tudhope SJ, Fenwick PS, et al. Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages[J]. Eur Respir J,2010,36(1):178-186.
5、 Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2010,23(4):235-256. Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2010,23(4):235-256.
6、 Kroegel C, Wirtz H. History of guidelines for the diagnosis and management of asthma: From opinion to control[J]. Drugs,2009,69(9):1189-1204. Kroegel C, Wirtz H. History of guidelines for the diagnosis and management of asthma: From opinion to control[J]. Drugs,2009,69(9):1189-1204.
7、 Peters-Golden M. Putting on the brakes: Cyclic amp as a multipronged controller of macrophage function[J]. Sci Signal,2009,2(75):37-42. Peters-Golden M. Putting on the brakes: Cyclic amp as a multipronged controller of macrophage function[J]. Sci Signal,2009,2(75):37-42.
8、 Aronoff DM, Canetti C, Peters-Golden M. Prostaglandin e2 inhibits alveolar macrophage phagocytosis through an e-prostanoid 2 receptor-mediated increase in intracellular cyclic amp[J]. J Immunol,2004,173(1):559-565. Aronoff DM, Canetti C, Peters-Golden M. Prostaglandin e2 inhibits alveolar macrophage phagocytosis through an e-prostanoid 2 receptor-mediated increase in intracellular cyclic amp[J]. J Immunol,2004,173(1):559-565.
9、 Pryzwansky KB, Kidao S, Merricks EP.compartmentalization of pde-4 and camp-dependent protein kinase in neutrophils and macrophages during phagocytosis[J]. Cell Biochem Biophys,1998,28(2-3):251-275. Pryzwansky KB, Kidao S, Merricks EP.compartmentalization of pde-4 and camp-dependent protein kinase in neutrophils and macrophages during phagocytosis[J]. Cell Biochem Biophys,1998,28(2-3):251-275.
10、 Ballinger MN, Welliver T, Straight S, et al. Transient increase in cyclic amp localized to macrophage phagosomes[J]. PLoS One,2010,5(11):e13962. Ballinger MN, Welliver T, Straight S, et al. Transient increase in cyclic amp localized to macrophage phagosomes[J]. PLoS One,2010,5(11):e13962.
11、 Rubins JB. Alveolar macrophages: Wielding the double-edged sword of inflammation[J]. Am J Respir Crit Care Med,2003,167(2):103-104. Rubins JB. Alveolar macrophages: Wielding the double-edged sword of inflammation[J]. Am J Respir Crit Care Med,2003,167(2):103-104.
12、 Winkler AR, Nocka KH, Sulahian TH, et al. In vitro modeling of human alveolar macrophage smoke exposure: Enhanced inflammation and impaired function[J]. Exp Lung Res,2008,34(9):599-629. Winkler AR, Nocka KH, Sulahian TH, et al. In vitro modeling of human alveolar macrophage smoke exposure: Enhanced inflammation and impaired function[J]. Exp Lung Res,2008,34(9):599-629.
13、 Liang Z, Zhang Q, Thomas CM, et al. Impaired macrophage phagocytosis of bacteria in severe asthma[J]. Respir Res,2014(15):72-83. Liang Z, Zhang Q, Thomas CM, et al. Impaired macrophage phagocytosis of bacteria in severe asthma[J]. Respir Res,2014(15):72-83.
14、 Serezani CH, Ballinger MN, Aronoff DM, et al. Cyclic amp: Master regulator of innate immune cell function[J]. Am J Respir Cell Mol Biol,2008,39(2):127-132. Serezani CH, Ballinger MN, Aronoff DM, et al. Cyclic amp: Master regulator of innate immune cell function[J]. Am J Respir Cell Mol Biol,2008,39(2):127-132.
15、 Soares AC, Souza DG, Pinho V, et al. Impaired host defense to klebsiella pneumoniae infection in mice treated with the pde4 inhibitor rolipram[J]. Br J Pharmacol,2003,140(5):855-862. Soares AC, Souza DG, Pinho V, et al. Impaired host defense to klebsiella pneumoniae infection in mice treated with the pde4 inhibitor rolipram[J]. Br J Pharmacol,2003,140(5):855-862.
上一篇
下一篇
出版者信息








《广州医药》公众号
目录