Segerer S, Henger A, Schmid H, Kretzler M, Draganovici D, Brandt U, Noessner E, Nelson P J, Kerjaschki D, Schlöndorff D, Regele H
Medizinische Poliklinik-Innenstadt, University of Munich, Germany.
Kidney Int. 2006 May;69(10):1765-73. doi: 10.1038/sj.ki.5000337.
Leukocyte infiltration, a hallmark of renal diseases, is orchestrated in part by the actions of chemokines. The chemokine CXCL8/interleukin (IL)-8 is expressed during renal diseases and allograft rejection, whereas the corresponding receptor CXCR1 has not been described previously. Expression of CXCR1 was characterized in peripheral blood using multicolor fluorescence-activated cell sorter analysis (FACS). CXCR1 was localized in 81 formalin-fixed, paraffin-embedded renal specimens by immunohistochemistry using a monoclonal antibody against human CXCR1. Included were biopsies with crescentic glomerulonephritis (CGN, n = 22), immunoglobulin (Ig) A nephropathy (n = 15), membranoproliferative glomerulonephritis (MPGN, n = 17), lupus nephritis (n = 12), membranous nephropathy (n = 11), and non-involved parts of tumor nephrectomies (n = 4). Consecutive tissue sections of human tonsils, allograft explants, and renal biopsies were stained for CD15- and CD68-positive cells. Expression of CXCR1 and CXCL8/IL-8 mRNA was quantified by real-time reverse transcriptase-polymerse chain reaction of microdissected renal biopsies (n = 35) of the same disease entities. By FACS CXCR1 expression was found on polymorphonuclear CXCR1 expression by polymorphonuclear leukocytes (PMNs), natural killer cells, and a subpopulation of monocytes. By immunohistochemistry, CXCR1 expression was found on infiltrating inflammatory cells (predominantly PMNs), as well as on intrinsic renal cells (arterial smooth muscle cells, endothelial cells of peritubular capillaries). The distribution pattern of CXCR1 differed between disease entities. The highest numbers of glomerular CXCR1-positive cells were present in biopsies with MPGN, followed by lupus nephritis, and CGN. CXCR1 might be involved in the recruitment of PMNs to the glomerular tuft, which could be targeted by CXCR1-blocking agents.
白细胞浸润是肾脏疾病的一个标志，部分由趋化因子的作用所调控。趋化因子CXCL8/白细胞介素（IL）-8在肾脏疾病和同种异体移植排斥反应期间表达，而相应的受体CXCR1此前尚未见报道。使用多色荧光激活细胞分选分析（FACS）在外周血中对CXCR1的表达进行了表征。通过使用抗人CXCR1单克隆抗体的免疫组织化学方法，在81份福尔马林固定、石蜡包埋的肾脏标本中定位了CXCR1。其中包括新月体性肾小球肾炎（CGN，n = 22）、免疫球蛋白（Ig）A肾病（n = 15）、膜增生性肾小球肾炎（MPGN，n = 17）、狼疮性肾炎（n = 12）、膜性肾病（n = 11）以及肿瘤肾切除术的未受累部分（n = 4）的活检标本。对人扁桃体、同种异体移植外植体和肾脏活检的连续组织切片进行CD15和CD68阳性细胞染色。通过对相同疾病实体的显微切割肾脏活检标本（n = 35）进行实时逆转录聚合酶链反应，对CXCR1和CXCL8/IL-8 mRNA的表达进行定量。通过FACS发现，多形核白细胞（PMN）、自然杀伤细胞和单核细胞亚群上存在CXCR1表达。通过免疫组织化学发现，CXCR1表达存在于浸润性炎症细胞（主要是PMN）以及肾脏固有细胞（动脉平滑肌细胞、肾小管周围毛细血管内皮细胞）上。CXCR1的分布模式在不同疾病实体之间存在差异。MPGN活检标本中肾小球CXCR1阳性细胞数量最多，其次是狼疮性肾炎和CGN。CXCR1可能参与PMN向肾小球毛细血管丛的募集，CXCR1阻断剂可能靶向于此。
