The 5-lipoxygenase product 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a potent eosinophil chemoattractant in vitro. To determine whether it is active in vivo, 5-oxo-ETE was administered intratracheally to BN rats and pulmonary eosinophils were immunostained with an antibody to major basic protein. 5-Oxo-ETE induced a dramatic increase in eosinophils, which reached maximal levels (5 times control) between 15 and 24 h following administration, and thereafter declined. LTB4 had a similar effect to 5-oxo-ETE but appeared to be somewhat less effective. In contrast, LTD4 and LTE4 were inactive. 5-Oxo-ETE-induced eosinophilia was inhibited by 75% following pretreatment of the animals with antibodies to integrins VLA-4 or LFA-1, but was not significantly inhibited by an antibody to Mac-1, nor after pretreatment with receptor antagonists to LTB4 (LY255283) or PAF (WEB 2170). These observations raise the possibility that 5-oxo-ETE may be an important physiological mediator in inflammatory diseases characterized with eosinophil recruitment, such as asthma.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.21646 |
| Date | January 1998 |
| Creators | Stamatiou, Panagiota. |
| Contributors | Martin, J. G. (advisor), Powell, W. S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650116, proquestno: MQ50886, Theses scanned by UMI/ProQuest. |
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