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Genetic factors determine the contribution of leukotrienes to acute inflammatory responses.

Publication ,  Journal Article
Goulet, JL; Byrum, RS; Key, ML; Nguyen, M; Wagoner, VA; Koller, BH
Published in: J Immunol
May 1, 2000

Leukotrienes (LT) are potent lipid mediators synthesized by the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LT have been implicated in a broad spectrum of inflammatory processes. To investigate the influence of genetic factors on the contribution of LT to acute inflammation, we generated congenic 5-lipoxygenase-deficient 129, C57BL/6 (B6), and DBA/1Lac (DBA) mouse lines. Topical application of AA evoked a vigorous inflammatory response in 129 and DBA mice, whereas only a modest response was seen in B6 animals. The response to AA in 129 and DBA strains is LT dependent. In contrast, LT make little contribution to this response in B6 mice. AA-induced inflammation in B6 mice is prostanoid dependent, since this response was substantially reduced by treating B6 mice with a cyclooxygenase inhibitor. These data suggest that prostanoids are essential for AA-induced cutaneous inflammation in B6 mice, whereas LT are the major mediators of this response in 129 and DBA strains. In contrast, the response to AA in the peritoneal cavity is robust in the 129 and B6 strains, but was significantly blunted in DBA mice, showing that strain differences in the response to AA are tissue specific. Variations in these and other experimental models of inflammation appear to correlate directly with the ability of a particular mouse strain and a specific tissue to respond to LT, specifically LTC4. Taken together, these findings indicate that the relative contribution of prostanoids and LT to inflammatory responses is variable not only between strains but also between different tissues within these inbred mouse lines.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2000

Volume

164

Issue

9

Start / End Page

4899 / 4907

Location

United States

Related Subject Headings

  • Zymosan
  • Species Specificity
  • Peritonitis
  • Mice, Mutant Strains
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Congenic
  • Mice
  • Leukotrienes
  • Leukotriene C4
 

Citation

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Goulet, J. L., Byrum, R. S., Key, M. L., Nguyen, M., Wagoner, V. A., & Koller, B. H. (2000). Genetic factors determine the contribution of leukotrienes to acute inflammatory responses. J Immunol, 164(9), 4899–4907. https://doi.org/10.4049/jimmunol.164.9.4899
Goulet, J. L., R. S. Byrum, M. L. Key, M. Nguyen, V. A. Wagoner, and B. H. Koller. “Genetic factors determine the contribution of leukotrienes to acute inflammatory responses.J Immunol 164, no. 9 (May 1, 2000): 4899–4907. https://doi.org/10.4049/jimmunol.164.9.4899.
Goulet JL, Byrum RS, Key ML, Nguyen M, Wagoner VA, Koller BH. Genetic factors determine the contribution of leukotrienes to acute inflammatory responses. J Immunol. 2000 May 1;164(9):4899–907.
Goulet, J. L., et al. “Genetic factors determine the contribution of leukotrienes to acute inflammatory responses.J Immunol, vol. 164, no. 9, May 2000, pp. 4899–907. Pubmed, doi:10.4049/jimmunol.164.9.4899.
Goulet JL, Byrum RS, Key ML, Nguyen M, Wagoner VA, Koller BH. Genetic factors determine the contribution of leukotrienes to acute inflammatory responses. J Immunol. 2000 May 1;164(9):4899–4907.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

May 1, 2000

Volume

164

Issue

9

Start / End Page

4899 / 4907

Location

United States

Related Subject Headings

  • Zymosan
  • Species Specificity
  • Peritonitis
  • Mice, Mutant Strains
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice, Congenic
  • Mice
  • Leukotrienes
  • Leukotriene C4