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.
Goulet
J L
JL
Department of Medicine, University of North Carolina, Chapel Hill 27599-7020.
Snouwaert
J N
JN
Latour
A M
AM
Coffman
T M
TM
Koller
B H
BH
D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D017997:Leukotriene C4 / Q000378:metabolism; D015289:Leukotrienes / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D015289:Leukotrienes; D010972:Platelet Activating Factor; D017997:Leukotriene C4; D013929:Thromboxane B2; D001094:Arachidonate 5-Lipoxygenase; D015232:Dinoprostone