Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung.

Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Research Abstract Details 

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Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Abstract Text:

BACKGROUND: Upregulation of matrix metalloproteinases (MMPs) has been associated with chronic lung allograft rejection known as bronchiolitis obliterans syndrome. It has been suggested that MMP inhibition could prevent the rejection response. However, the effect of MMP inhibition on lung allograft rejection has not been reported. METHODS: Utilizing a rat model of lung transplantation, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were overexpressed by gene therapy in F344 rat lung allografts prior to transplantation into WKY recipient rats. Separately, WKY rats that received F344 lung allografts were treated systemically with COL-3, a global MMP inhibitor. RESULTS: TIMP-1 and TIMP-2 had differential effects on delayed type hypersensitivity (DTH) responses to donor antigens and type V collagen, an autoantigen involved in the rejection response. Neither TIMP-1 or TIMP-2 affected the onset of rejection pathology. COL-3 suppressed DTH responses to donor antigens and type V collagen, abrogated local production of tumor necrosis factor-alpha, and interleukin-1beta. Although it did not prevent rejection pathology, COL-3 (30 mg/kg) induced intragraft B cell hyperplasia suggestive of posttransplant proliferative disorder (PTLD). CONCLUSIONS: These data identify a complex role for MMPs and TIMPs in the immunopathogenesis of lung allograft rejection, and indicate their effects are not limited to matrix remodeling.

Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Publishing Authors By Initials

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Transplantation

VOLUME: 83

Page Numbers: 799-808

Journal Abbreviation:

ISSN: 0041-1337

DAY: 27

MONTH: Mar

YEAR: 2007

Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 132144

Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: metabolism

Chemical & Substance for Abstract: Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung. Information

Substance Name: Matrix Metalloproteinases

Registry Number: EC 3.4.24.-

Grant and Affiliation Information for Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung.

AFFILIATION: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL081350

ACRONYM: HL

MEDLINETA: Transplantation

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