Lung transplant ischemia reperfusion injury: Metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-α expression

Takekazu Iwata, Masako Chiyo, Shigetoshi Yoshida, Gerald N. Smith, Elizabeth A. Mickler, Robert Presson, Amanda J. Fisher, David Brand, Oscar W. Cummings, David S. Wilkes

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background. Immunity to type V collagen [col(V)] contributes to lung transplant rejection. Matrix metalloproteases (MMPs), which are induced by transplant-related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local IRI-induced inflammation. Methods. To test the hypothesis that MMPs induce col(V) exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor, COL-3, before inducing lung IRI without transplantation, and in parallel studies, Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and postisograft lung transplantation. Results. Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and upregulated tumor necrosis factor-α. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-α; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. Conclusion.MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalTransplantation
Volume85
Issue number3
DOIs
StatePublished - Feb 1 2008

Fingerprint

Collagen Type V
Metalloproteases
Chemotaxis
Reperfusion Injury
Oncogenes
Neutrophils
Down-Regulation
Tumor Necrosis Factor-alpha
Transplants
Lung
Growth
Lung Transplantation
Bronchoalveolar Lavage
Tissue Donors
Isografts
Inflammation
Inbred WKY Rats
Inhibition (Psychology)
Graft Rejection
Immunity

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Lung transplant ischemia reperfusion injury : Metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-α expression. / Iwata, Takekazu; Chiyo, Masako; Yoshida, Shigetoshi; Smith, Gerald N.; Mickler, Elizabeth A.; Presson, Robert; Fisher, Amanda J.; Brand, David; Cummings, Oscar W.; Wilkes, David S.

In: Transplantation, Vol. 85, No. 3, 01.02.2008, p. 417-426.

Research output: Contribution to journalArticle

Iwata, Takekazu ; Chiyo, Masako ; Yoshida, Shigetoshi ; Smith, Gerald N. ; Mickler, Elizabeth A. ; Presson, Robert ; Fisher, Amanda J. ; Brand, David ; Cummings, Oscar W. ; Wilkes, David S. / Lung transplant ischemia reperfusion injury : Metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-α expression. In: Transplantation. 2008 ; Vol. 85, No. 3. pp. 417-426.
@article{95ffd64ac592459ebd8264a8ce1b7ecb,
title = "Lung transplant ischemia reperfusion injury: Metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-α expression",
abstract = "Background. Immunity to type V collagen [col(V)] contributes to lung transplant rejection. Matrix metalloproteases (MMPs), which are induced by transplant-related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local IRI-induced inflammation. Methods. To test the hypothesis that MMPs induce col(V) exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor, COL-3, before inducing lung IRI without transplantation, and in parallel studies, Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and postisograft lung transplantation. Results. Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and upregulated tumor necrosis factor-α. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-α; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. Conclusion.MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.",
author = "Takekazu Iwata and Masako Chiyo and Shigetoshi Yoshida and Smith, {Gerald N.} and Mickler, {Elizabeth A.} and Robert Presson and Fisher, {Amanda J.} and David Brand and Cummings, {Oscar W.} and Wilkes, {David S.}",
year = "2008",
month = "2",
day = "1",
doi = "10.1097/TP.0b013e31815e91b6",
language = "English (US)",
volume = "85",
pages = "417--426",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Lung transplant ischemia reperfusion injury

T2 - Metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-α expression

AU - Iwata, Takekazu

AU - Chiyo, Masako

AU - Yoshida, Shigetoshi

AU - Smith, Gerald N.

AU - Mickler, Elizabeth A.

AU - Presson, Robert

AU - Fisher, Amanda J.

AU - Brand, David

AU - Cummings, Oscar W.

AU - Wilkes, David S.

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Background. Immunity to type V collagen [col(V)] contributes to lung transplant rejection. Matrix metalloproteases (MMPs), which are induced by transplant-related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local IRI-induced inflammation. Methods. To test the hypothesis that MMPs induce col(V) exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor, COL-3, before inducing lung IRI without transplantation, and in parallel studies, Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and postisograft lung transplantation. Results. Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and upregulated tumor necrosis factor-α. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-α; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. Conclusion.MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.

AB - Background. Immunity to type V collagen [col(V)] contributes to lung transplant rejection. Matrix metalloproteases (MMPs), which are induced by transplant-related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local IRI-induced inflammation. Methods. To test the hypothesis that MMPs induce col(V) exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor, COL-3, before inducing lung IRI without transplantation, and in parallel studies, Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and postisograft lung transplantation. Results. Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and upregulated tumor necrosis factor-α. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-α; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. Conclusion.MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.

UR - http://www.scopus.com/inward/record.url?scp=40049111092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40049111092&partnerID=8YFLogxK

U2 - 10.1097/TP.0b013e31815e91b6

DO - 10.1097/TP.0b013e31815e91b6

M3 - Article

C2 - 18322435

AN - SCOPUS:40049111092

VL - 85

SP - 417

EP - 426

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 3

ER -