Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models

Liying Liu, Erbin Dai, Leslie Miller, Bruce Seet, Alshad Lalani, Colin Macauley, Xing Li, Herbert W. Virgin, Campbell Bunce, Peter Turner, Richard Moyer, Douglas McFadden, Alexandra Lucas

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background. Both CC and CXC chemokines direct monocyte and T-cell migration and activation at sites of vascular injury, but the relative contributions of each chemokine class to transplant vasculopathy development have not been defined. The nonselective C, CC, and CXC chemokine binding protein, M-T7, inhibits vasculopathy development after angioplasty and after renal transplant. We have assessed the effects of three viral chemokine-binding proteins with differing ranges of chemokine inhibition on plaque growth in rats after aortic allograft transplant. Methods. One of two myxomaviral chemokine binding proteins, (1) M-T1, a selective CC chemokine inhibitor, of (2) M-T7, a nonselective chemokine-binding protein, was given immediately after transplant. A separate group was treated with the γ68-herpesvirus protein, M3, a C, CC, CXC, and CX3C binding protein, with preferential CC binding. Results. Intimal hyperplasia was significantly reduced at late times posttransplant after infusion of each chemokine-binding protein (P≤0.05). Early inhibition of macrophage and T-cell invasion was associated with a late decrease in vasculopathy development. Infusion of an inactive myxomavirus protein did not inhibit plaque growth. Combined high-dose M-T1 and M-T7 did not reduce plaque growth or early cell invasion to a greater extent than either protein alone. Coinfusion of the CC chemokines macrophage chemoattractant protein-1 and macrophage inflammatory protein-1α neutralized M-T1 and M-T7 inhibition of monocyte invasion, respectively, suggesting a key role for CC chemokine-mediated cellular influx. Conclusion. Viral chemokine-modulating proteins effectively reduce aortic allograft vasculopathy, acting predominantly through inhibition of a CC chemokine-mediated response.

Original languageEnglish (US)
Pages (from-to)1652-1660
Number of pages9
JournalTransplantation
Volume77
Issue number11
DOIs
StatePublished - Jun 15 2004
Externally publishedYes

Fingerprint

CC Chemokines
Chemokines
Allografts
Carrier Proteins
Transplants
CXC Chemokines
Proteins
Monocytes
C Chemokines
Growth
Macrophages
Tunica Intima
T-Lymphocytes
Macrophage Inflammatory Proteins
Herpesviridae
Vascular System Injuries
Chemotactic Factors
Angioplasty
Cell Movement
Hyperplasia

ASJC Scopus subject areas

  • Transplantation

Cite this

Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models. / Liu, Liying; Dai, Erbin; Miller, Leslie; Seet, Bruce; Lalani, Alshad; Macauley, Colin; Li, Xing; Virgin, Herbert W.; Bunce, Campbell; Turner, Peter; Moyer, Richard; McFadden, Douglas; Lucas, Alexandra.

In: Transplantation, Vol. 77, No. 11, 15.06.2004, p. 1652-1660.

Research output: Contribution to journalArticle

Liu, L, Dai, E, Miller, L, Seet, B, Lalani, A, Macauley, C, Li, X, Virgin, HW, Bunce, C, Turner, P, Moyer, R, McFadden, D & Lucas, A 2004, 'Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models', Transplantation, vol. 77, no. 11, pp. 1652-1660. https://doi.org/10.1097/01.TP.0000131173.52424.84
Liu, Liying ; Dai, Erbin ; Miller, Leslie ; Seet, Bruce ; Lalani, Alshad ; Macauley, Colin ; Li, Xing ; Virgin, Herbert W. ; Bunce, Campbell ; Turner, Peter ; Moyer, Richard ; McFadden, Douglas ; Lucas, Alexandra. / Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models. In: Transplantation. 2004 ; Vol. 77, No. 11. pp. 1652-1660.
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abstract = "Background. Both CC and CXC chemokines direct monocyte and T-cell migration and activation at sites of vascular injury, but the relative contributions of each chemokine class to transplant vasculopathy development have not been defined. The nonselective C, CC, and CXC chemokine binding protein, M-T7, inhibits vasculopathy development after angioplasty and after renal transplant. We have assessed the effects of three viral chemokine-binding proteins with differing ranges of chemokine inhibition on plaque growth in rats after aortic allograft transplant. Methods. One of two myxomaviral chemokine binding proteins, (1) M-T1, a selective CC chemokine inhibitor, of (2) M-T7, a nonselective chemokine-binding protein, was given immediately after transplant. A separate group was treated with the γ68-herpesvirus protein, M3, a C, CC, CXC, and CX3C binding protein, with preferential CC binding. Results. Intimal hyperplasia was significantly reduced at late times posttransplant after infusion of each chemokine-binding protein (P≤0.05). Early inhibition of macrophage and T-cell invasion was associated with a late decrease in vasculopathy development. Infusion of an inactive myxomavirus protein did not inhibit plaque growth. Combined high-dose M-T1 and M-T7 did not reduce plaque growth or early cell invasion to a greater extent than either protein alone. Coinfusion of the CC chemokines macrophage chemoattractant protein-1 and macrophage inflammatory protein-1α neutralized M-T1 and M-T7 inhibition of monocyte invasion, respectively, suggesting a key role for CC chemokine-mediated cellular influx. Conclusion. Viral chemokine-modulating proteins effectively reduce aortic allograft vasculopathy, acting predominantly through inhibition of a CC chemokine-mediated response.",
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T1 - Viral chemokine-binding proteins inhibit inflammatory responses and aortic allograft transplant vasculopathy in rat models

AU - Liu, Liying

AU - Dai, Erbin

AU - Miller, Leslie

AU - Seet, Bruce

AU - Lalani, Alshad

AU - Macauley, Colin

AU - Li, Xing

AU - Virgin, Herbert W.

AU - Bunce, Campbell

AU - Turner, Peter

AU - Moyer, Richard

AU - McFadden, Douglas

AU - Lucas, Alexandra

PY - 2004/6/15

Y1 - 2004/6/15

N2 - Background. Both CC and CXC chemokines direct monocyte and T-cell migration and activation at sites of vascular injury, but the relative contributions of each chemokine class to transplant vasculopathy development have not been defined. The nonselective C, CC, and CXC chemokine binding protein, M-T7, inhibits vasculopathy development after angioplasty and after renal transplant. We have assessed the effects of three viral chemokine-binding proteins with differing ranges of chemokine inhibition on plaque growth in rats after aortic allograft transplant. Methods. One of two myxomaviral chemokine binding proteins, (1) M-T1, a selective CC chemokine inhibitor, of (2) M-T7, a nonselective chemokine-binding protein, was given immediately after transplant. A separate group was treated with the γ68-herpesvirus protein, M3, a C, CC, CXC, and CX3C binding protein, with preferential CC binding. Results. Intimal hyperplasia was significantly reduced at late times posttransplant after infusion of each chemokine-binding protein (P≤0.05). Early inhibition of macrophage and T-cell invasion was associated with a late decrease in vasculopathy development. Infusion of an inactive myxomavirus protein did not inhibit plaque growth. Combined high-dose M-T1 and M-T7 did not reduce plaque growth or early cell invasion to a greater extent than either protein alone. Coinfusion of the CC chemokines macrophage chemoattractant protein-1 and macrophage inflammatory protein-1α neutralized M-T1 and M-T7 inhibition of monocyte invasion, respectively, suggesting a key role for CC chemokine-mediated cellular influx. Conclusion. Viral chemokine-modulating proteins effectively reduce aortic allograft vasculopathy, acting predominantly through inhibition of a CC chemokine-mediated response.

AB - Background. Both CC and CXC chemokines direct monocyte and T-cell migration and activation at sites of vascular injury, but the relative contributions of each chemokine class to transplant vasculopathy development have not been defined. The nonselective C, CC, and CXC chemokine binding protein, M-T7, inhibits vasculopathy development after angioplasty and after renal transplant. We have assessed the effects of three viral chemokine-binding proteins with differing ranges of chemokine inhibition on plaque growth in rats after aortic allograft transplant. Methods. One of two myxomaviral chemokine binding proteins, (1) M-T1, a selective CC chemokine inhibitor, of (2) M-T7, a nonselective chemokine-binding protein, was given immediately after transplant. A separate group was treated with the γ68-herpesvirus protein, M3, a C, CC, CXC, and CX3C binding protein, with preferential CC binding. Results. Intimal hyperplasia was significantly reduced at late times posttransplant after infusion of each chemokine-binding protein (P≤0.05). Early inhibition of macrophage and T-cell invasion was associated with a late decrease in vasculopathy development. Infusion of an inactive myxomavirus protein did not inhibit plaque growth. Combined high-dose M-T1 and M-T7 did not reduce plaque growth or early cell invasion to a greater extent than either protein alone. Coinfusion of the CC chemokines macrophage chemoattractant protein-1 and macrophage inflammatory protein-1α neutralized M-T1 and M-T7 inhibition of monocyte invasion, respectively, suggesting a key role for CC chemokine-mediated cellular influx. Conclusion. Viral chemokine-modulating proteins effectively reduce aortic allograft vasculopathy, acting predominantly through inhibition of a CC chemokine-mediated response.

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