title: Different roles for matrix metalloproteinase-2 and matrix metalloproteinase-9 in the pathogenesis of cardiac allograft rejection.
abstract: Recent studies have shown an increased expression of several matrix metalloproteinases (MMP) during cardiac, renal and pulmonary allograft rejection. To further define the roles of MMP-2 and MMP-9 in the pathogenesis of cardiac allograft rejection, BALB/c cardiac allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Allografts rejected by wild-type mice revealed a significant increase in MMP-2 and MMP-9 expression. MMP-2-deficiency significantly prolonged allograft survival time. Functioning allografts harvested from MMP-2-/- mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-2+/+ mice at the same time. In contrast, MMP-9-deficiency significantly decreased allograft survival time. Functioning allografts harvested from MMP-9+/+ mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-9-/- mice at the same time. MMP-2-/- recipients showed decreased T-cell alloreactivity mediated by a defect in dendritic cell stimulatory and T-cell responsive capacities. In contrast, MMP-9-/- recipients showed increased T-cell alloreactivity mediated by a significant increased in dendritic cell stimulatory and T-cell responsive capacities. These results indicate that MMP2 and MMP-9 play significantly different roles in the process of cardiac allograft rejection.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Lacey G
authors.initials: LG
authors.lastname: Campbell
authors.forename: Sabarinathan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: J Michael
authors.initials: JM
authors.lastname: Shipley
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rogers
authors.forename: Nader
authors.initials: N
authors.lastname: Moazami
authors.forename: Robert M
authors.initials: RM
authors.lastname: Senior
authors.forename: Andrés
authors.initials: A
authors.lastname: Jaramillo
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000201:enzymology* / Q000209:etiology; D016027:Heart Transplantation; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9