Takaeda Masayoshi, Yokoyama Hitoshi, Segawa-Takaeda Chikako, Wada Takashi, Kobayashi Ken-ichi
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
Am J Nephrol. 2002 Jan-Feb;22(1):48-57. doi: 10.1159/000046674.
To clarify the characteristics of high endothelial venule (HEV) -like vessels in the interstitium of human glomerulonephritis, we investigated the expression of HEVs related molecules such as P-selectin and L-selectin ligands; MECA-79 epitope and variant sulfated forms of sialyl Lewis X (variant sLe(X), clones 2H5, 2F3, GS-13 and GS-36) in kidney specimens by means of immunohistochemical studies, and P-selectin and hevin mRNA signals by using in situ hybridization analyses. In lymphoid organs, HEVs strongly expressed P-selectin, MECA-79, variant sLe(X) and hevin mRNA signals. In normal kidneys (n = 4), only P-selectin was faintly positive in the vessels of interstitium, but other molecules could not be detected. Interstitial P-selectin expression was upregulated in patients with tubulointerstitial diseases (n = 4) and proliferative glomerulonephritis (n = 51) such as IgA-related nephropathy (n = 39), membranoproliferative glomerulonephritis (n = 4) and crescentic glomerulonephritis (n = 2), but not in nonproliferative glomerular diseases (n = 39) such as minimal change nephrotic syndrome (n = 18) (1.00 +/- 0.41, 0.64 +/- 0.11, 0.21 +/- 0.05, respectively). Interstitial P-selectin expression also correlated with interstitial local cellular infiltration (r = 0.60, p < 0.0001). In addition, P-selectin mRNA signals were detected on the peritubular capillaries and HEV-like vascular endothelial cells. MECA-79 and variant sLe(X) (2H5 and 2F3) were weakly expressed on the HEV-like vessels located at the corticomedullary regions in three cases (7%) and in nine cases (27%) with interstitial cellular infiltration, respectively. However, we could not detect GS-13, GS-36 or hevin mRNA signals in the diseased kidney specimens. In conclusion, HEV-like vessels in renal interstitium expressed molecules somewhat different from HEVs in lymphoid organs and were associated with interstitial leukocyte accumulation in human proliferative glomerulonephritis possibly through the de novo expression of P-selectin and partly L-selectin ligands (MECA-79 epitope and variant sLe(X)) in the interstitial lesions.
为了阐明人类肾小球肾炎间质中高内皮微静脉（HEV）样血管的特征，我们通过免疫组织化学研究，调查了肾脏标本中HEV相关分子的表达，如P-选择素和L-选择素配体；MECA-79表位以及唾液酸化路易斯X的变异硫酸化形式（变异sLe(X)，克隆2H5、2F3、GS-13和GS-36），并通过原位杂交分析检测P-选择素和hevin mRNA信号。在淋巴器官中，HEV强烈表达P-选择素、MECA-79、变异sLe(X)和hevin mRNA信号。在正常肾脏（n = 4）中，仅间质血管中的P-选择素呈弱阳性，但未检测到其他分子。在肾小管间质疾病患者（n = 4）和增殖性肾小球肾炎患者（n = 51）如IgA相关性肾病（n = 39）、膜增生性肾小球肾炎（n = 4）和新月体性肾小球肾炎（n = 2）中，间质P-选择素表达上调，但在非增殖性肾小球疾病患者（n = 39）如微小病变肾病综合征（n = 18）中未上调（分别为1.00±0.41、0.64±0.11、0.21±0.05）。间质P-选择素表达也与间质局部细胞浸润相关（r = 0.60，p < 0.0001）。此外，在肾小管周围毛细血管和HEV样血管内皮细胞上检测到P-选择素mRNA信号。在3例（7%）位于皮质髓质区域的HEV样血管以及9例（27%）有间质细胞浸润的病例中，MECA-79和变异sLe(X)（2H5和2F3）呈弱阳性表达。然而，在患病肾脏标本中未检测到GS-13、GS-36或hevin mRNA信号。总之，肾间质中的HEV样血管表达的分子与淋巴器官中的HEV有所不同，并且在人类增殖性肾小球肾炎中可能通过间质病变中P-选择素以及部分L-选择素配体（MECA-79表位和变异sLe(X)）的从头表达与间质白细胞积聚相关。
