Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice

J. L. Goulet, R. C. Griffiths, Phillip Ruiz, R. B. Mannon, P. Flannery, J. L. Platt, B. H. Koller, T. M. Coffman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range of biologic activities. Previous studies, using pharmacological agents to inhibit LT synthesis or activity, have implicated these eicosanoids in transplant rejection. To further investigate the role of LTs in acute graft rejection, we transplanted kidneys from CByD2F1, mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene. Unexpectedly, allograft rejection was significantly accelerated in 5-LO-deficient mice compared with wild-type animals. Despite the marked reduction in graft survival, the 5lo mutation had no effect on the hemodynamics or morphology of the allografts. Although LTB4 levels were reduced, renal thromboxane B2 production and cytokine expression were not altered in 5-LO-deficient allograft recipients. These findings suggest that, along with their proinflammatory actions, metabolites of 5-LO can act to enhance allograft survival.

Original languageEnglish
Pages (from-to)6631-6636
Number of pages6
JournalJournal of Immunology
Volume167
Issue number11
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

Arachidonate 5-Lipoxygenase
Leukotrienes
Allografts
Kidney
Graft Rejection
129 Strain Mouse
Thromboxane B2
Mutation
Wild Animals
Leukotriene B4
Eicosanoids
Graft Survival
Arachidonic Acid
Hemodynamics
Pharmacology
Cytokines
Lipids
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Goulet, J. L., Griffiths, R. C., Ruiz, P., Mannon, R. B., Flannery, P., Platt, J. L., ... Coffman, T. M. (2001). Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. Journal of Immunology, 167(11), 6631-6636.

Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. / Goulet, J. L.; Griffiths, R. C.; Ruiz, Phillip; Mannon, R. B.; Flannery, P.; Platt, J. L.; Koller, B. H.; Coffman, T. M.

In: Journal of Immunology, Vol. 167, No. 11, 01.12.2001, p. 6631-6636.

Research output: Contribution to journalArticle

Goulet, JL, Griffiths, RC, Ruiz, P, Mannon, RB, Flannery, P, Platt, JL, Koller, BH & Coffman, TM 2001, 'Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice', Journal of Immunology, vol. 167, no. 11, pp. 6631-6636.
Goulet JL, Griffiths RC, Ruiz P, Mannon RB, Flannery P, Platt JL et al. Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. Journal of Immunology. 2001 Dec 1;167(11):6631-6636.
Goulet, J. L. ; Griffiths, R. C. ; Ruiz, Phillip ; Mannon, R. B. ; Flannery, P. ; Platt, J. L. ; Koller, B. H. ; Coffman, T. M. / Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. In: Journal of Immunology. 2001 ; Vol. 167, No. 11. pp. 6631-6636.
@article{891946b510be4b588a3db5dbeefe6d85,
title = "Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice",
abstract = "Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range of biologic activities. Previous studies, using pharmacological agents to inhibit LT synthesis or activity, have implicated these eicosanoids in transplant rejection. To further investigate the role of LTs in acute graft rejection, we transplanted kidneys from CByD2F1, mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene. Unexpectedly, allograft rejection was significantly accelerated in 5-LO-deficient mice compared with wild-type animals. Despite the marked reduction in graft survival, the 5lo mutation had no effect on the hemodynamics or morphology of the allografts. Although LTB4 levels were reduced, renal thromboxane B2 production and cytokine expression were not altered in 5-LO-deficient allograft recipients. These findings suggest that, along with their proinflammatory actions, metabolites of 5-LO can act to enhance allograft survival.",
author = "Goulet, {J. L.} and Griffiths, {R. C.} and Phillip Ruiz and Mannon, {R. B.} and P. Flannery and Platt, {J. L.} and Koller, {B. H.} and Coffman, {T. M.}",
year = "2001",
month = "12",
day = "1",
language = "English",
volume = "167",
pages = "6631--6636",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice

AU - Goulet, J. L.

AU - Griffiths, R. C.

AU - Ruiz, Phillip

AU - Mannon, R. B.

AU - Flannery, P.

AU - Platt, J. L.

AU - Koller, B. H.

AU - Coffman, T. M.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range of biologic activities. Previous studies, using pharmacological agents to inhibit LT synthesis or activity, have implicated these eicosanoids in transplant rejection. To further investigate the role of LTs in acute graft rejection, we transplanted kidneys from CByD2F1, mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene. Unexpectedly, allograft rejection was significantly accelerated in 5-LO-deficient mice compared with wild-type animals. Despite the marked reduction in graft survival, the 5lo mutation had no effect on the hemodynamics or morphology of the allografts. Although LTB4 levels were reduced, renal thromboxane B2 production and cytokine expression were not altered in 5-LO-deficient allograft recipients. These findings suggest that, along with their proinflammatory actions, metabolites of 5-LO can act to enhance allograft survival.

AB - Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range of biologic activities. Previous studies, using pharmacological agents to inhibit LT synthesis or activity, have implicated these eicosanoids in transplant rejection. To further investigate the role of LTs in acute graft rejection, we transplanted kidneys from CByD2F1, mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene. Unexpectedly, allograft rejection was significantly accelerated in 5-LO-deficient mice compared with wild-type animals. Despite the marked reduction in graft survival, the 5lo mutation had no effect on the hemodynamics or morphology of the allografts. Although LTB4 levels were reduced, renal thromboxane B2 production and cytokine expression were not altered in 5-LO-deficient allograft recipients. These findings suggest that, along with their proinflammatory actions, metabolites of 5-LO can act to enhance allograft survival.

UR - http://www.scopus.com/inward/record.url?scp=0035576010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035576010&partnerID=8YFLogxK

M3 - Article

C2 - 11714834

AN - SCOPUS:0035576010

VL - 167

SP - 6631

EP - 6636

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -