Altered inflammatory responses in leukotriene-deficient mice.
Leukotrienes have been implicated in the regulation of immune responses, including inflammation and immediate hypersensitivity reactions. Here, we describe the phenotypic analysis of leukotriene-deficient mice generated by inactivation of the 5-lipoxygenase (5LO) gene. These 5LO(-/-) mice were unable to synthesize detectable levels of leukotrienes and were more resistant to lethal anaphylaxis induced by platelet-activating factor. The intensity of an acute inflammatory response induced by arachidonic acid was similar in 5LO(-/-) mice and controls. However, the response in 5LO(-/-) mice, but not in controls, could be virtually eliminated by a cyclooxygenase inhibitor. These data suggest that inflammatory responses are modulated by arachidonic acid metabolites through a variety of interconnected mechanisms. This has important implications for understanding the early events of an inflammatory response and for designing drugs for use in therapeutic intervention.[1]References
- Altered inflammatory responses in leukotriene-deficient mice. Goulet, J.L., Snouwaert, J.N., Latour, A.M., Coffman, T.M., Koller, B.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
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