Mackiewicz Z, Rimkevicius A, Petersen J, Andersen C B, Dudek E, Vytrasova M, Konttinen Y T
Department of Pathology, Vilnius University Institute of Experimental and Clinical Medicine, Lithuania.
Ann Rheum Dis. 2005 Aug;64(8):1229-32. doi: 10.1136/ard.2004.027029.
To analyse some scavenging related molecules in Wegener's granulomatosis (WG) macrophages.
Immunohistochemical staining of lung, nasopharynx, and skin for macrophage markers related to scavenging (macrophage scavenger receptor MARCO, collagenase-1 and gelatinase-B), formation of multinuclear foreign body giant cells (ADAM 9/meltrin-gamma and ADAM 12/meltrin-alpha), and cell debris derived from neutrophils, endothelial cells and mast cells (specific granule protein 28 (SGP28), von Willebrand factor (vWF) and mast cell tryptase, respectively). TechMate staining robot and biotin-streptavidin protocol were used.
Some macrophages were activated and expressed collagenase-1 and gelatinase-B. Approximately 5% of macrophages expressed scavenger receptor, whereas 20-30% were meltrin positive. Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix. Lymphocytic follicles with germinal centres were found in the same areas.
In WG tissue lesions macrophage and giant cells seem to be overwhelmed by the bulk to be scavenged. Despite cellular activation and continuing maturation to professional scavenger receptor (MARCO) and meltrin positive multinuclear giant cells combined with an organisation into granulomas, macrophages still contain partially undigested cell and tissue rests. This necrotic and damaged self may be the driving force for the formation of giant cell ("foreign body") granulomas. This, together with the local formation of secondary lymphatic follicles (with germinal centres), indicates active local antigen processing and presentation.
分析韦格纳肉芽肿（WG）巨噬细胞中一些与清除相关的分子。
对肺、鼻咽和皮肤进行免疫组织化学染色，检测与清除相关的巨噬细胞标志物（巨噬细胞清道夫受体MARCO、胶原酶-1和明胶酶-B）、多核异物巨细胞的形成（ADAM 9/解整合素金属蛋白酶γ和ADAM 12/解整合素金属蛋白酶α）以及源自中性粒细胞、内皮细胞和肥大细胞的细胞碎片（分别为特异性颗粒蛋白28（SGP28）、血管性血友病因子（vWF）和肥大细胞类胰蛋白酶）。使用TechMate染色机器人和生物素-链霉亲和素协议。
一些巨噬细胞被激活并表达胶原酶-1和明胶酶-B。约5%的巨噬细胞表达清道夫受体，而20 - 30%为解整合素金属蛋白酶阳性。间质和肉芽肿相关的巨噬细胞及巨细胞含有部分未消化的、免疫反应性的SGP28、vWF和类胰蛋白酶阳性的细胞残余物以及胶原基质。在相同区域发现了有生发中心的淋巴细胞滤泡。
在WG组织病变中，巨噬细胞和巨细胞似乎被大量待清除物质所淹没。尽管细胞被激活并持续成熟为专业清道夫受体（MARCO）和解整合素金属蛋白酶阳性的多核巨细胞，并形成肉芽肿，但巨噬细胞仍含有部分未消化的细胞和组织残余物。这种坏死和受损的自身物质可能是巨细胞（“异物”）肉芽肿形成的驱动力。这与局部二级淋巴滤泡（有生发中心）的形成一起，表明存在活跃的局部抗原处理和呈递。
