Published online before print May 8, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1002477

Received for publication October 2, 2002.
Revised February 11, 2003.
Accepted for publication February 14, 2003.

Article

5-Lipoxygenase knockout mice exhibit a resistance to pleurisy and lung injury caused by carrageenan

Salvatore Cuzzocrea ^*, Antonietta Rossi , Ivana Serraino ^*, Emanuela Mazzon , Rosanna Di Paola ^*, Laura Dugo ^*, Tiziana Genovese ^*, Barbara Calabrò ^*, Achille P. Caputi ^*, and Lidia Sautebin

Departments of *Clinical and Experimental Medicine and Pharmacology andDepartment of Experimental Pharmacology, University "Federico II", Napoli, Italy; andBiomorphology, School of Medicine, University of Messina Torre Biologica, Policlinico Universitario, Italy

Abstract

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.

Key Words: adhesion molecules • inflammation

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