The role of 5-lipoxygenase and leukotrienes in shock and ischemia-reperfusion injury.
The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia-reperfusion injury.
Rossi
Antonietta
A
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. antrossi@unina.it
Pergola
Carlo
C
Cuzzocrea
Salvatore
S
Sautebin
Lidia
L
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D051379:Mice; D015427:Reperfusion Injury / Q000378:metabolism*; D012769:Shock / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase