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PMID: 9854052 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 102 ·No. 12 ·1998-12-15 ·Pages 2165-72

Stamatiou P, Hamid Q, Taha R, Yu W, Issekutz TB, Rokach J, Khanapure SP, Powell WS

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.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology Antigens, CD/metabolism Arachidonic Acids/administration & dosage,pharmacology Chemotactic Factors/pharmacology Immunohistochemistry Integrin alpha4 Integrins/metabolism Intubation, Intratracheal/methods Leukotrienes/pharmacology Lung/cytology,drug effects Macrophage-1 Antigen/metabolism Male Platelet Activating Factor/pharmacology Pulmonary Eosinophilia/chemically induced Rats Time Factors
Chemicals
Antibodies, Monoclonal Antigens, CD Arachidonic Acids Chemotactic Factors Integrins Leukotrienes Macrophage-1 Antigen Platelet Activating Factor 5-oxo-6,8,11,14-eicosatetraenoic acid Integrin alpha4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Stamatiou P
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.
Hamid Q
Taha R
Yu W
Issekutz T B
Rokach J
Khanapure S P
Powell W S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI1995
Published
1998-12-15
Pages
2165-72
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC509171
Subset
IM
Grants
NIDDK NIH HHS · DK-44730 · United States
External Links
PubMed source DOI: 10.1172/JCI1995 PMC Full Text View journal details
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