Rastaldi Maria Pia, Ferrario Franco, Crippa Andor, Dell'antonio Giacomo, Casartelli Donatella, Grillo Carlo, D'Amico Giuseppe
Renal Immunopathology Center, San Carlo Borromeo Hospital, Milan, Italy.
Department of Pathology, San Raffaele Hospital, Milan, Italy.
J Am Soc Nephrol. 2000 Nov;11(11):2036-2043. doi: 10.1681/ASN.V11112036.
Although it is widely known that many macrophages are present in glomeruli of antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis (ANCA + RV) and are believed to contribute to necrotizing extracapillary damage, their precise role is not yet completely understood, especially in humans. The goal of this study was to provide evidence of glomerular macrophage properties in human vasculitis. Twenty-five renal biopsies of ANCA + RV and 18 cases of cryoglobulinemic glomerulonephritis (cryoGN), a disease characterized by massive glomerular macrophage infiltration but absence of necrotizing extracapillary lesions, were selected, and macrophage number, adhesion, acute activation, proliferation, and apoptosis were analyzed by immunohistochemistry and in situ hybridization. Accumulation of macrophages in ANCA + RV was found in areas of glomerular active lesions, whereas in cryoGN, they homogeneously occupied the entire glomerular tuft. Considering the areas of accumulation, comparable macrophage numbers were detected in both diseases. Glomerular vascular cell adhesion molecule-1 was found only in ANCA + RV and only in areas of active lesions. Acute macrophage activation (HLA class II, 27E10) and proinflammatory cytokine production (tumor necrosis factor-alpha, interleukin-1alpha) were prominent in ANCA + RV, whereas in cryoGN, 30% of glomerular macrophages seemed activated and cytokine expression was limited to a few glomerular cells (P: = 0.01). Moreover, only in ANCA + RV proliferative markers were shown on glomerular macrophages and apoptotic macrophages were found. From the data, it seems that ANCA + RV and cryoGN differ profoundly in macrophage properties, namely adhesion, proliferation, and apoptotic clearance. Moreover, acute activation and cytokine production seem to be present in a greater number of macrophages in ANCA + RV, giving this disease a stronger severity that could be taken into account for therapeutic strategies.
尽管众所周知，许多巨噬细胞存在于抗中性粒细胞胞浆抗体（ANCA）阳性肾血管炎（ANCA+RV）的肾小球中，并且被认为促成了坏死性毛细血管外损伤，但其确切作用尚未完全明了，尤其是在人类中。本研究的目的是提供人类血管炎中肾小球巨噬细胞特性的证据。选取了25例ANCA+RV肾活检标本和18例冷球蛋白血症性肾小球肾炎（cryoGN）病例，后者以大量肾小球巨噬细胞浸润但无坏死性毛细血管外病变为特征，通过免疫组织化学和原位杂交分析巨噬细胞数量、黏附、急性活化、增殖和凋亡情况。在ANCA+RV中，巨噬细胞在肾小球活动性病变区域积聚，而在cryoGN中，它们均匀地占据整个肾小球丛。考虑到积聚区域，两种疾病中检测到的巨噬细胞数量相当。仅在ANCA+RV的活动性病变区域发现肾小球血管细胞黏附分子-1。急性巨噬细胞活化（HLA II类，27E10）和促炎细胞因子产生（肿瘤坏死因子-α、白细胞介素-1α）在ANCA+RV中显著，而在cryoGN中，30%的肾小球巨噬细胞似乎被活化，细胞因子表达仅限于少数肾小球细胞（P=0.01）。此外，仅在ANCA+RV中，肾小球巨噬细胞显示增殖标记，并且发现了凋亡巨噬细胞。从这些数据来看，ANCA+RV和cryoGN在巨噬细胞特性，即黏附、增殖和凋亡清除方面似乎有很大差异。此外，急性活化和细胞因子产生似乎在ANCA+RV中更多的巨噬细胞中存在，使得这种疾病具有更强的严重性，这在治疗策略中应予以考虑。
