Correspondence

Leukotrienes

N Engl J Med 2008; 358:746February 14, 2008

Article

To the Editor:

Peters-Golden and Henderson (Nov. 1 issue)1 review the role of the 5-lipoxygenase pathway of arachidonate metabolism and of leukotrienes, a product of that pathway, in asthma, cardiovascular disease, and cancer. The authors conclude that leukotrienes “probably play a role in other diseases,” and we would like to add that they do so in end-stage renal disease. Peripheral-blood mononuclear-cell 5-lipoxygenase activity is involved in low-density lipoprotein oxidation during the early phases of atherogenesis.2,3 We4 and others5 have demonstrated that 5-lipoxygenase activity and expression are up-regulated in peripheral-blood mononuclear cells from patients with uremia who are undergoing maintenance hemodialysis. The subsequent increase in membrane lipid peroxidation, reactive-oxygen-species production, low-density lipoprotein oxidation, mitochondrial damage, and apoptosis of peripheral-blood mononuclear cells seems to contribute to the increased susceptibility to atherosclerosis and coronary heart disease in patients with uremia, as compared with the age-matched general population. The activity of 5-lipoxygenase is inhibited by vitamin E and other natural antioxidants in peripheral-blood mononuclear-cell membranes and in vitro3,4,6; the specific inhibition of 5-lipoxygenase may confirm, from a biochemical point of view, the good results obtained with antioxidant supplementation in patients undergoing hemodialysis.4,6

Massimo Taccone-Gallucci, M.D.
Simone Manca-di-Villahermosa, M.D.
Tor Vergata University, 00169 Rome, Italy
taccone.gallucci@med.uniroma2.it

Mauro Maccarrone, Ph.D.
University of Teramo, 64100 Teramo, Italy

6 References

1. 1

   Peters-Golden M, Henderson WR Jr. Leukotrienes. N Engl J Med 2007;357:1841-1854
   Full Text | Web of Science | Medline

2. 2

   Takahashi Y, Zhu H, Yoshimoto T. Essential roles of lipoxygenases in LDL oxidation and development of atherosclerosis. Antioxid Redox Signal 2005;7:425-431
   CrossRef | Web of Science | Medline

3. 3

   Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress and inflammation. Annu Rev Nutr 2005;25:151-174
   CrossRef | Web of Science | Medline

4. 4

   Maccarrone M, Manca di Villahermosa S, Giacominelli-Stuffler R, Taccone-Gallucci M. Vitamin E, 5-lipoxygenase and kidney disease. In: Bellock OH, ed. New topics in vitamin E research. New York: Nova Science, 2006:111-32.
   

5. 5

   Menegatti E, Roccatello D, Rossi D, Formica M, Piccoli G, Sena LM. 5-Lipoxygenase gene expression in hemodialysis. Artif Organs 1998;22:140-142
   CrossRef | Web of Science | Medline

6. 6

   Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M. N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int 2006;69:1450-1454
   Web of Science | Medline

Author/Editor Response

In response to the comments of Taccone-Gallucci and colleagues, space limitations precluded us from discussing the activation of the 5-lipoxygenase pathway in end-stage renal disease and many other conditions.

Taccone-Gallucci and colleagues call attention to the possibility that, like other oxygenases, 5-lipoxygenase can mediate disease independently of leukotriene synthesis through its generation of reactive oxygen intermediates and its contribution to tissue oxidant stress,1 which in turn can influence inflammation, cell survival, and transcription-factor activation.2,3

Marc Peters-Golden, M.D.
University of Michigan, Ann Arbor, MI 48109
petersm@umich.edu

William R. Henderson, Jr., M.D.
University of Washington, Seattle, WA 98109

3 References

1. 1

   Swindle EJ, Coleman JW, DeLeo FR, Metcalfe DD. FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent. J Immunol 2007;179:7059-7071
   Web of Science | Medline

2. 2

   Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol 2005;25:1332-1340
   CrossRef | Web of Science | Medline

3. 3

   Bonizzi G, Piette J, Schoonbroodt S, et al. Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. Mol Cell Biol 1999;19:1950-1960
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Valerio Chiurchiù, Mauro Maccarrone. (2011) Chronic Inflammatory Disorders and Their Redox Control: From Molecular Mechanisms to Therapeutic Opportunities. Antioxidants & Redox Signaling 15:9, 2605-2641
   CrossRef