The long pentraxin Ptx3 is synthesized in IgA glomerulonephritis and activates mesangial cells
The long pentraxin Ptx3 is synthesized in IgA glomerulonephritis and activates mesangial cells
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DOI：
10.4049/jimmunol.170.3.1466
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发表时间：
2003-02-01
影响因子：
4.4
通讯作者：
Camussi, G
中科院分区：
文献类型：
--
作者：
Bussolati, B;Peri, G;Camussi, G
长戊甲素PTX3最近参与了炎症反应的放大和先天免疫的调节。在本研究中，我们评估了PTX3在肾小球炎症中的表达及其作用。研究了PTX3在IgA、I型膜增生性和弥漫性增生性狼疮性肾小球肾炎（主要由常驻系膜细胞驱动的炎症和增生性病变）和膜性肾小球肾炎和局灶节段性肾小球硬化（通常没有肾小球炎症征象）中的表达。我们在IgA肾小球肾炎患者的肾活检中发现PTX3在扩大的系膜区呈强烈染色。肾小球系膜细胞和内皮细胞染色。在I型膜增生性肾小球肾炎的肾小球中也可见散在的ptx3阳性细胞。CD14的同时表达提示这些细胞的炎症起源。其他肾小球肾病患者的正常肾组织和活检中PTX3在肾小球中主要呈阴性表达。然而，ptx3阳性细胞在表现为炎症间质损伤的肾病间质中检测到。体外培养的人系膜细胞在tnf - α和IgA刺激下合成PTX3，并对重组PTX3表现出特异性结合。此外，外源性PTX3刺激可促进系膜细胞收缩和促炎脂质介质血小板活化因子的合成。总之，我们提供了第一个证据，证明系膜细胞既可以产生PTX3，也可以成为PTX3的靶标。在肾小球肾炎患者的肾组织中检测到这种长戊曲霉素提示其在调节肾小球和肾小管损伤中的潜在作用。
The long pentraxin PTX3 has been recently involved in amplification of the inflammatory reactions and regulation of innate immunity. In the present study we evaluated the expression and role of PTX3 in glomerular inflammation. PTX3 expression was investigated in the IgA, type I membranoproliferative, and diffuse proliferative lupus glomerulonephritis, which are characterized by inflammatory and proliferative lesions mainly driven by resident mesangial cells, and in the membranous glomerulonephritis and the focal segmental glomerular sclerosis, where signs of glomerular inflammation are usually absent. We found an intense staining for PTX3 in the expanded mesangial areas of renal biopsies obtained from patients with IgA glomerulonephritis. The pattern of staining was on glomerular mesangial and endothelial cells. Scattered PTX3-positive cells were also detected in glomeruli of type I membranoproliferative glomerulonephritis. The concomitant expression of CD14 suggests an inflammatory origin of these cells. Normal renal tissue and biopsies from patients with the other glomerular nephropathies studied were mainly negative for PTX3 expression in glomeruli. However, PTX3-positive cells were detected in the interstitium of nephropathies showing inflammatory interstitial injury. In vitro, cultured human mesangial cells synthesized PTX3 when stimulated with TNF-alpha and IgA and exhibited specific binding for recombinant PTX3. Moreover, stimulation with exogenous PTX3 promoted mesangial cell contraction and synthesis of the proinflammatory lipid mediator platelet-activating factor. In conclusion, we provide the first evidence that mesangial cells may both produce and be a target for PTX3. The detection of this long pentraxin in the renal tissue of patients with glomerulonephritis suggests its potential role in the modulation of glomerular and tubular injury.