Adiponectin and Its Globular Fragment Differentially Modulate the Oxidative Burst of Primary Human Phagocytes
Adiponectin and Its Globular Fragment Differentially Modulate the Oxidative Burst of Primary Human Phagocytes
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DOI：
10.1016/j.ajpath.2011.10.013
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发表时间：
2012-02-01
影响因子：
6
通讯作者：
Marie, Jean-Claude
中科院分区：
文献类型：
--
作者：
Chedid, Pia;Hurtado-Nedelec, Margarita;Marie, Jean-Claude
脂联素（Acrp 30）属于C1 q/肿瘤坏死因子α（TNF α）相关蛋白家族。Acrp 30作为高、中、低分子量的多聚体循环。在这项研究中，我们检测了Acrp 30及其球状片段（gAcrp 30）从类风湿关节炎患者的滑液。有趣的是，LMW形式在类风湿性关节炎患者和健康受试者的滑液中比血清中更丰富。我们还研究了Acrp 30和gAcrp 30通过吞噬NADPH氧化酶对活性氧（ROS）产生的影响。Acrp 30抑制fMLF诱导的人吞噬细胞的ROS产生，而gAcrp 30增强它。gAcrp 30的作用与TNF α相加，而Acrp 30抑制TNF α诱导的引发。gAcrp 30增强了NOX-2在质膜上的表达，伴随着p47（phox）磷酸化的增加。p38丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶1（ERK 1）/2的选择性抑制剂可通过gAcrp 30消除p47（phox）磷酸化。与此相反，p47（phox）磷酸化抑制Acrp 30与增加AMP激活蛋白激酶（AMPK）磷酸化在吞噬细胞。这些结果表明，人类吞噬细胞活性氧的产生是由不同的机制，选择性Acrp 30与gAcrp 30。gAcrp 30和更高分子量的Acrp 30亚型之间的不平衡可能通过调节NADPH氧化酶而导致慢性炎症。(Am J Pathol 2012，180：682-692; DOI：10.1016/j.ajpath.2011.10.013）
Adiponectin (Acrp30) belongs to the family of C1q/tumor necrosis factor alpha (TNF alpha)-related proteins. Acrp30 circulates as multimers of high, middle, and low molecular weight. In this study, we detected Acrp30 and its globular fragment (gAcrp30) in synovial fluid from rheumatoid arthritis patients. Intriguingly, the LMW form was more abundant in synovial fluid than in serum from both rheumatoid arthritis patients and healthy subjects. We also investigated the effects of Acrp30 and gAcrp30 on reactive oxygen species (ROS) production via the phagocytic NADPH oxidase. Acrp30 inhibited fMLF-induced ROS production by human phagocytes, whereas gAcrp30 enhanced it. gAcrp30's effect is additive with TNF alpha, whereas Acrp30 inhibited TNF alpha-induced priming. gAcrp30 enhanced NOX-2 expression at the plasma membrane, with a concomitant increase in p47(phox) phosphorylation. Selective inhibitors of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1 (ERK1)/2 abrogated p47(phox) phosphorylation by gAcrp30. In contrast, p47(phox) phosphorylation was inhibited by Acrp30 in association with increased AMP-activated protein kinase (AMPK) phosphorylation in phagocytes. These results suggest that human phagocyte ROS production is regulated by different mechanisms selective for Acrp30 versus gAcrp30. An imbalance between gAcrp30 and higher molecular weight isoforms of Acrp30 might contribute to chronic inflammation by regulating NADPH oxidase. (Am J Pathol 2012, 180: 682-692; DOI: 10.1016/j.ajpath.2011.10.013)