Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies
Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies
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DOI：
10.1007/s10157-004-0292-0
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发表时间：
2004-06
期刊：
影响因子：
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通讯作者：
Saeed R. Khan
中科院分区：
文献类型：
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作者：
Saeed R. Khan
草酸钙（CaOx），磷酸钙（CaP）和尿酸或尿酸盐是肾脏中最常见的晶体。大多数晶体引起炎症反应，导致纤维化、肾单位丢失，最终导致慢性肾衰竭。在这三者中，CaOx一水合物是最具反应性的，而某些形式的CaP不引起任何可辨别的反应。活性氧在晶体和肾细胞之间的相互作用过程中产生，并负责各种细胞反应。CaOx晶体通常在肾小管中形成。肾上皮细胞暴露于CaOx晶体导致骨桥蛋白、bikunin、硫酸乙酰肝素、单核细胞趋化蛋白1（MCP-1）和前列腺素（PG）E2的合成增加，已知它们参与炎症过程和细胞外基质产生。CaOx晶体在大鼠肾脏中的沉积也激活了肾素-血管紧张素系统。Ox和CaOx晶体都选择性激活暴露的肾小管细胞中的p38促分裂原活化蛋白激酶（MAPK）。CaP晶体可在肾小管腔、肾小管细胞或肾小管基底膜中形成。暴露于透钙磷石晶体的肾上皮细胞产生MCP-1。碱性CaP和焦磷酸钙二水合物诱导成纤维细胞中的有丝分裂，刺激PGE 2的产生，并上调金属蛋白酶（MMP）的合成，同时通过激活p42/44 MAPK下调MMP抑制剂的产生。肾脏中尿酸盐结晶的沉积与肾小管萎缩、间质纤维化和炎症浸润的发展相关。暴露于尿酸晶体的肾上皮细胞合成MCP-1以及PGE 2。接触尿酸盐晶体的单核细胞或中性粒细胞产生肿瘤坏死因子α、白细胞介素-1（IL-1）、IL-6和IL-8。IL-8的表达通过细胞外信号调节激酶1（ERK-1）/ERK-2和核转录因子活化蛋白1和核因子κβ介导。尿酸盐晶体还刺激巨噬细胞产生MMPs。
Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin–angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor α, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor κβ. Urate crystals also stimulate the macrophages to produce MMPs.