Hou F F, Reddan D N, Seng W K, Owen W F
Division of Nephrology, Nanfang Hospital, Guangzhou, Peoples Republic of China.
Semin Dial. 2001 Mar-Apr;14(2):135-9. doi: 10.1046/j.1525-139x.2001.00034.x.
beta(2)-microglobulin (beta(2)M) amyloidosis (A beta(2)M) is a serious, often incapacitating complication for patients undergoing long-term hemodialysis. Amyloid deposits composed of beta(2)M fibrils as the major constituent protein are mainly localized in joints and periarticular bone and lead to chronic arthralgias, carpal tunnel syndrome, and eventually destructive arthropathy. Although recent histologic studies have shown the accumulation of monocytes/macrophages around amyloid deposits, the factor(s) causing their infiltration and pathologic involvement have yet to be fully elucidated. Immunohistochemical staining reveals that macrophages in tenosynovial tissues express CD13, CD14, CD33, HLA-DR, and CD68 antigens on their surfaces and express interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6. Many of these cells also express LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49d/CD29) on their surfaces. AGE-modified beta(2)M enhances chemotaxis of monocytes and stimulates macrophages to release bone-resorbing cytokines, such as IL-1 beta, TNF-alpha and IL-6. Via a RAGE-mediated pathway, AGE-modified, but not unmodified beta(2)M, significantly delays constitutive apoptosis of human peripheral blood monocytes. Monocytes survival in an advanced glycation end product (AGE) beta(2)M-containing microenvironment is associated with their phenotypic alteration into macrophage-like cells that generate more reactive oxygen species and elaborate greater quantities of IL-1 beta and TNF-alpha. Thus through regulation of their survival and differentiation, AGE beta(2)M in amyloid deposits may be able to influence the presence and quantity of infiltrated monocytes, and hence their biologic effects.
β2-微球蛋白（β2M）淀粉样变性（Aβ2M）是长期血液透析患者严重的、常导致功能丧失的并发症。由β2M原纤维作为主要组成蛋白构成的淀粉样沉积物主要位于关节和关节周围骨骼，导致慢性关节痛、腕管综合征，并最终发展为破坏性关节病。尽管最近的组织学研究表明淀粉样沉积物周围有单核细胞/巨噬细胞积聚，但导致它们浸润和病理参与的因素尚未完全阐明。免疫组织化学染色显示，腱鞘组织中的巨噬细胞表面表达CD13、CD14、CD33、HLA-DR和CD68抗原，并表达白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和IL-6。这些细胞中的许多还在其表面表达淋巴细胞功能相关抗原-1（LFA-1，CD11a/CD18）、巨噬细胞抗原-1（Mac-1，CD11b/CD18）和极迟抗原-4（VLA-4，CD49d/CD29）。糖基化终产物修饰的β2M增强单核细胞的趋化性，并刺激巨噬细胞释放骨吸收细胞因子，如IL-1β、TNF-α和IL-6。通过一种晚期糖基化终末产物受体（RAGE）介导的途径，糖基化终产物修饰而非未修饰的β2M显著延迟人外周血单核细胞的组成性凋亡。单核细胞在含有晚期糖基化终末产物（AGE）β2M的微环境中的存活与其向巨噬细胞样细胞的表型改变有关，后者产生更多的活性氧并分泌更多量的IL-1β和TNF-α。因此，通过调节其存活和分化，淀粉样沉积物中的AGEβ2M可能能够影响浸润单核细胞的存在和数量，从而影响其生物学效应。
