Yagnik Darshna
Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, London NW4 4BT, UK.
Int J Inflam. 2014;2014:526496. doi: 10.1155/2014/526496. Epub 2014 Sep 24.
Human blood derived in vitro differentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants from in vitro differentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF) 1.54 ± 0.10 mean ± SEM; ng/mL per 10(6) cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFα suppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFα secretion 0.7 ± 0.06 mean ± SEM; ng/mL per 10(6) cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation.
多年来，人们一直在研究源自人血体外分化的单核细胞或巨噬细胞，以确定这些细胞在痛风消退阶段所起的作用。巨噬细胞能够吞噬单水尿酸钠（MSU）晶体而不释放炎症因子。本研究分析了巨噬细胞血小板活化因子的分泌及其在痛风消退途径中的可能作用。对用MSU晶体刺激的体外分化巨噬细胞的上清液分析显示，血小板活化因子（PAF）的分泌量为1.54±0.10（平均值±标准误）；每10⁶个细胞中ng/mL。同样处理的未成熟单核细胞中没有这种分泌。当这些单核细胞用重组人PAF-乙酰水解酶（rhuPAF-AH）预处理后，MSU晶体导致肿瘤坏死因子α（TNFα）受到抑制。向用MSU晶体处理的分化巨噬细胞中添加血小板活化因子（PAF）拮抗剂WEB2086，可使TNFα分泌量增加至0.7±0.06（平均值±标准误）；每10⁶个细胞中ng/mL。本研究确定了PAF和PAF受体拮抗剂在巨噬细胞摄取MSU晶体并消除伴随炎症的途径中的作用。
