III.Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Kidney Int. 2013 May;83(5):865-77. doi: 10.1038/ki.2012.483. Epub 2013 Jan 23.
Matrix metalloproteinase 9 (MMP9) is a conditionally expressed enzyme and is upregulated in glomerulonephritis. Its function in these diseases, however, remains to be fully elucidated. The induction of nephrotoxic serum nephritis (NTN) in wild-type mice resulted in an upregulation of MMP9, followed by leukocyte infiltration, albuminuria, and subsequent renal failure. MMP9 deficiency ameliorated the course of NTN as indicated by reduced histological injury and reduced infiltration of proinflammatory macrophages. The chemotaxis of MMP9-deficient macrophages in vitro was impaired. Intrarenal macrophages isolated from the kidneys of nephritic MMP9 knockout mice still displayed the typical features of a proinflammatory phenotype and were indistinguishable from wild type-derived cells. Bone marrow transplantation restored renal tissue injury and macrophage recruitment when wild type-derived donor cells were transplanted onto MMP9-deficient mice prior to the induction of NTN. Thus, leukocyte-derived MMP9 mediates the recruitment of proinflammatory macrophages into kidneys during experimental crescentic glomerulonephritis.
基质金属蛋白酶 9（MMP9）是一种条件表达的酶，在肾小球肾炎中上调。然而，其在这些疾病中的功能仍有待充分阐明。在野生型小鼠中诱导肾毒性血清肾炎（NTN）导致 MMP9 的上调，随后白细胞浸润、白蛋白尿和随后的肾衰竭。MMP9 缺乏症通过减少组织损伤和减少炎症性巨噬细胞浸润来改善 NTN 的病程。体外 MMP9 缺陷型巨噬细胞的趋化作用受损。从肾炎 MMP9 基因敲除小鼠肾脏中分离的肾内巨噬细胞仍然表现出典型的炎症表型特征，与野生型衍生细胞无法区分。骨髓移植在 NTN 诱导前将野生型衍生供体细胞移植到 MMP9 缺陷型小鼠中时，恢复了肾组织损伤和巨噬细胞募集。因此，白细胞衍生的 MMP9 介导了实验性新月体肾小球肾炎中促炎巨噬细胞向肾脏的募集。
