Chen XS, Sheller JR, Johnson EN, Funk CD:
Role of leukotrienes revealed by targeted disruption of the
5-lipoxygenase gene.
Nature 1994 Nov 10;372(6502):179-82
ABSTRACT
Leukotrienes constitute a class of potent biological mediators of
inflammation and anaphylaxis (for reviews see refs 1 and 2). Their
biosynthesis derives from 5-lipoxygenase-catalysed oxygenation of
arachidonic acid in granulocytes, macrophages and mast cells. To
examine the physiological importance of leukotrienes, we have
disrupted the 5-lipoxygenase gene by homologous recombination in
embryonic stem cells. 5-Lipoxygenase-deficient (5LX-/-) mice develop
normally and are healthy. They show a selective opposition to
certain inflammatory insults. Although there is no difference in
their reaction to endotoxin shock, the 5LX-/- animals resist the
lethal effects of shock induced by platelet-activating factor.
Reaction to ear inflammation induced by phorbol ester is normal,
whereas inflammation induced by arachidonic acid is markedly
reduced. Contrasts were also found in two models of leukocyte
chemotaxis in vivo. The phenotype of 5LX-/- mice under injurious
insult identifies the role for leukotrienes in the pathophysiology
of select inflammatory states.
