5-Lipoxygenase knockout mice exhibit a resistance to pleurisy and lung injury caused by carrageenan.
In the present study, by comparing the responses in wild-type (WT) mice and mice lacking [knockout (KO)] the 5-lipoxygenase (5-LO), we investigated the role played by 5-LO in the development of acute inflammation. When compared with carragenan-treated 5-LOWT mice, 5-LOKO mice, which had received carrageenan, exhibited a reduced degree of pleural exudation, polymorphonuclear cell migration. Lung myeloperoxidase activity, an index of neutrophil infiltration, was significantly reduced in 5-LOKO mice in comparison with 5-LOWT. Lung-tissue sections from carrageenan-treated 5-LOWT mice showed positive staining for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, which were mainly localized around vessels. The intensity and degree of ICAM-1, VCAM-1, P-selectin, and E-selectin were markedly reduced in tissue section from carrageenan-5-LOKO mice, which also improved the histological status of the inflamed lungs. Taken together, our results clearly demonstrate that 5-LO modulates neutrophil infiltration in the acute lung inflammation.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine, University Federico II, Napoli, Italy. salvator@unime.it
Rossi
Antonietta
A
Serraino
Ivana
I
Mazzon
Emanuela
E
Di Paola
Rosanna
R
Dugo
Laura
L
Genovese
Tiziana
T
Calabrò
Barbara
B
Caputi
Achille P
AP
Sautebin
Lidia
L
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D002351:Carrageenan; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000096:biosynthesis; D010998:Pleurisy / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D015815:Cell Adhesion Molecules; D009569:Nitric Oxide; D002351:Carrageenan; D001094:Arachidonate 5-Lipoxygenase