Leukocyte-derived MMP9 is crucial for the recruitment of proinflammatory macrophages in experimental glomerulonephritis.
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.
III.Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Malte A
MA
Kluger
Gunther
G
Zahner
Hans-Joachim
HJ
Paust
Melanie
M
Schaper
Tim
T
Magnus
Ulf
U
Panzer
Rolf A K
RA
Stahl
D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D018450:Disease Progression; D005921:Glomerulonephritis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D013997:Time Factors
D018925:Chemokines; D018836:Inflammation Mediators; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse