Segerer Stephan, Cui Yan, Hudkins Kelly L, Goodpaster Tracy, Eitner Frank, Mack Matthias, Schlöndorff Detlef, Alpers Charles E
Department of Pathology, University of Washington, Seattle, Washington.
Medizinische Klinik II, Klinikum der Rheinisch-Westfaelischen Technischen Hoshschule, Aachen, Germany.
J Am Soc Nephrol. 2000 Dec;11(12):2231-2242. doi: 10.1681/ASN.V11122231.
Crescents are morphologic manifestations of severe glomerular injury. Several chemokines and their receptors have been demonstrated to be involved in animal models of crescentic glomerulonephritis (cGN) and are potential targets for therapeutic interventions. Therefore, the expression of monocyte chemoattractant protein-1 (MCP-1), its receptor chemokine receptor 2B (CCR2B), and CCR5 in human cGN was studied. MCP-1 and CCR2B mRNA expression was evaluated, by in situ hybridization, in serial sections of 23 renal biopsies from patients with cGN. T cells, macrophages, and CCR5-expressing cells were examined by immunohistochemical analysis. MCP-1 mRNA was expressed by cells in crescents, parietal epithelium, and tubular epithelium, as well as by infiltrating leukocytes in the tubulointerstitium. The expression of CCR2B mRNA was observed in cells in glomeruli and crescents and in infiltrating leukocytes in the tubulointerstitium. CCR2B mRNA expression could not be clearly localized to intrinsic renal cells; evidence that most of the CCR2B-expressing cells were leukocytes is provided. CD3-positive T cells formed the major part of the interstitial cell infiltrates but were rare within the glomerular tufts. CD68-positive macrophages constituted a major population of infiltrating cells in crescents and contributed significantly to the interstitial infiltrates. The number of glomerular macrophages was associated with the number of MCP-1- and CCR2B-positive glomerular cells. Expression of CCR2B was significantly correlated with interstitial CD3-positive T cells. CCR5 expression was restricted to infiltrating leukocytes and was correlated quantitatively and by localization with interstitial CD3-positive T cells and CD68-positive macrophages. These first morphologic data on the distribution of CCR2-positive cells in human cGN suggest differential effects of chemokines and their receptors on the distribution of infiltrating leukocytes in different compartments of the kidney.
新月体是严重肾小球损伤的形态学表现。几种趋化因子及其受体已被证明参与新月体性肾小球肾炎（cGN）的动物模型，并且是治疗干预的潜在靶点。因此，研究了单核细胞趋化蛋白-1（MCP-1）、其受体趋化因子受体2B（CCR2B）和CCR5在人类cGN中的表达。通过原位杂交评估了23例cGN患者肾活检连续切片中MCP-1和CCR2B mRNA的表达。通过免疫组织化学分析检测T细胞、巨噬细胞和表达CCR5的细胞。MCP-1 mRNA由新月体、壁层上皮和肾小管上皮中的细胞表达，以及由肾小管间质中的浸润白细胞表达。在肾小球和新月体中的细胞以及肾小管间质中的浸润白细胞中观察到CCR2B mRNA的表达。CCR2B mRNA的表达不能明确定位于肾固有细胞；提供了证据表明大多数表达CCR2B的细胞是白细胞。CD3阳性T细胞构成间质细胞浸润的主要部分，但在肾小球丛中很少见。CD68阳性巨噬细胞构成新月体中浸润细胞的主要群体，并对间质浸润有显著贡献。肾小球巨噬细胞的数量与MCP-1和CCR2B阳性肾小球细胞的数量相关。CCR2B的表达与间质CD3阳性T细胞显著相关。CCR5的表达仅限于浸润白细胞，并且在数量和定位上与间质CD3阳性T细胞和CD68阳性巨噬细胞相关。这些关于人类cGN中CCR2阳性细胞分布的首批形态学数据表明趋化因子及其受体对肾不同部位浸润白细胞分布的不同影响。
