van den Born J, van den Heuvel L P, Bakker M A, Veerkamp J H, Assmann K J, Weening J J, Berden J H
Department of Medicine, University of Nijmegen, The Netherlands.
Kidney Int. 1993 Feb;43(2):454-63. doi: 10.1038/ki.1993.67.
Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve different glomerulopathies. Four normal kidney specimens served as controls. A homogenous to linear staining of the GBM was observed in the normal kidney with anti-HSPG-core mAb (JM-72) and anti-HS mAb (JM-403). In human glomerulopathies the major alteration was a segmental or total absence of GBM staining with anti-HS mAb JM-403, which is most pronounced in lupus nephritis, membranous glomerulonephritis (GN), minimal change disease and diabetic nephropathy, whereas the HSPG-core staining by mAb JM-72 was unaltered. In addition we found HSPG-core protein in the mesangial matrix when this was increased in membranoproliferative GN Type I, Schönlein-Henoch GN, IgA nephropathy, lupus nephritis, diabetic nephropathy and in focal glomerulosclerosis. Also staining with the anti-HS mAb JM-403 became positive within the mesangium, although to a lesser extent. Furthermore, amyloid deposits in AL and AA amyloidosis clearly stained with anti-HSPG-core mAb JM-72, and to a lesser degree with anti-HS mAb JM-403. Finally, in membranous GN (stage II and III), the GBM staining with anti-HSPG-core mAb JM-72 became irregular or granular, probably related to the formation of spikes. In conclusion, major alterations were observed in the glomerular distribution of HS and HSPG-core in various human glomerulopathies. The mAbs can be useful to further delineate the significance of HSPG and HS for glomerular diseases.
我们使用识别人类肾小球基底膜硫酸乙酰肝素蛋白聚糖（HSPG）核心蛋白或硫酸乙酰肝素（HS）侧链的单克隆抗体（mAb），在人类肾脏组织的冷冻切片上研究了它们在肾小球中的分布。该研究涉及95例活检，包括12种不同的肾小球病。4例正常肾脏标本作为对照。在正常肾脏中，抗HSPG核心mAb（JM - 72）和抗HS mAb（JM - 403）观察到肾小球基底膜呈均匀至线性染色。在人类肾小球病中，主要改变是抗HS mAb JM - 403对肾小球基底膜染色呈节段性或完全缺失，这在狼疮性肾炎、膜性肾小球肾炎（GN）、微小病变病和糖尿病肾病中最为明显，而mAb JM - 72对HSPG核心的染色未改变。此外，当膜增生性GN I型、过敏性紫癜性GN、IgA肾病、狼疮性肾炎、糖尿病肾病和局灶性肾小球硬化症中系膜基质增加时，我们在系膜基质中发现了HSPG核心蛋白。用抗HS mAb JM - 403染色在系膜内也呈阳性，尽管程度较轻。此外，AL和AA淀粉样变性中的淀粉样沉积物用抗HSPG核心mAb JM - 72染色明显，用抗HS mAb JM - 403染色程度较轻。最后，在膜性GN（II期和III期）中，抗HSPG核心mAb JM - 72对肾小球基底膜的染色变得不规则或呈颗粒状，可能与钉突形成有关。总之，在各种人类肾小球病中观察到HS和HSPG核心在肾小球分布上的主要改变。这些单克隆抗体有助于进一步阐明HSPG和HS对肾小球疾病的意义。
