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Research Article Free access | 10.1172/JCI1995

5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats.

P Stamatiou, Q Hamid, R Taha, W Yu, T B Issekutz, J Rokach, S P Khanapure, and W S Powell

Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.

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Published December 15, 1998 - More info

Published in Volume 102, Issue 12 on December 15, 1998
J Clin Invest. 1998;102(12):2165–2172. https://doi.org/10.1172/JCI1995.
© 1998 The American Society for Clinical Investigation
Published December 15, 1998 - Version history
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Abstract

We have shown previously that the 5-lipoxygenase product 5-oxo-6,8, 11,14-eicosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattractant in vitro. To determine whether this substance can induce pulmonary eosinophil infiltration in vivo, it was administered to Brown Norway rats by tracheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-Oxo-ETE induced a dramatic increase in the numbers of eosinophils (ED50, 2.5 microg) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then declined. LTB4 also induced pulmonary eosinophil infiltration with a similar ED50 but appeared to be somewhat less effective. In contrast, LTD4 and LTE4 were inactive. 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB4 and PAF antagonists LY255283 and WEB 2170, respectively. However, it was inhibited by approximately 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-1). In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway rats, raising the possibility that it may be a physiological mediator of inflammation in asthma.

Version history
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