Sean Eardley Kevin, Cockwell Paul
Department of Nephrology, University Hospital Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Kidney Int. 2005 Aug;68(2):437-55. doi: 10.1111/j.1523-1755.2005.00422.x.
Macrophages and progressive tubulointerstitial disease. In chronic renal disease, tubulointerstitial inflammation and injury is associated with infiltrating macrophages. As a consequence of primary injury, proteinuria, chronic hypoxia, and glomerular-derived cytokines may all differentially modulate the expression of factors that promote macrophage recruitment. In addition to adhesion molecules and chemokines, products of complement system and renin-angiotensin system activation may direct this process. Once present at interstitial sites, macrophages interact with resident cells and extracellular matrix to generate a proinflammatory microenvironment that amplifies tissues injury and promotes scarring. There is now increasing evidence for the efficacy of interventions directed against factors that recruit, activate, or are produced by macrophages. A detailed understanding of the biology of this area may lead to the further development of therapies that will improve the outcome of renal disease.
巨噬细胞与进行性肾小管间质疾病。在慢性肾脏疾病中,肾小管间质炎症和损伤与浸润的巨噬细胞有关。作为原发性损伤的结果,蛋白尿、慢性缺氧和肾小球源性细胞因子可能都会不同程度地调节促进巨噬细胞募集的因子的表达。除了黏附分子和趋化因子外,补体系统和肾素-血管紧张素系统激活的产物也可能指导这一过程。一旦巨噬细胞出现在间质部位,它们就会与驻留细胞和细胞外基质相互作用,产生促炎微环境,从而放大组织损伤并促进瘢痕形成。现在越来越多的证据表明,针对募集、激活巨噬细胞或由巨噬细胞产生的因子的干预措施是有效的。对该领域生物学的详细了解可能会促使进一步开发改善肾脏疾病预后的治疗方法。