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9- and 13-hydroxy-linoleic acid possess chemotactic activity for bovine and human polymorphonuclear leukocytes
P A Henricks1, F Engels, H van der Vliet
1Department of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Abstract:
The presence of polymorphonuclear leukocytes (PMNs) within the airways is a characteristic feature of a variety of lung diseases. Pulmonary alveolar macrophages (PAMs) and epithelial cells release many different factors which contribute to the recruitment of inflammatory cells into infected airways. PAMs and tracheal epithelial cells are able to produce linoleic acid metabolites (9-HODE and 13-HODE) besides arachidonic acid metabolites. The objective of the present study was to determine whether 9-HODE and 13-HODE possess chemotactic activity for isolated PMNs. It was found that 9-HODE and 13-HODE induced a chemotactic response of both human and bovine PMNs in vitro. The HODEs evoked chemotaxis with a linear dose response from 10(-10) to 10(-6) M to the same extent as the arachidonic acid metabolite 15-HETE. At 10(-8) M, 9-HODE and 13-HODE were approximately half as potent in inducing chemotaxis as compared to LTB4.
Insights
Linoleic acid metabolites, 9-HODE and 13-HODE, attract inflammatory cells called polymorphonuclear leukocytes (PMNs) to the airways. These compounds show significant chemotactic activity, potentially playing a role in lung inflammation.
Area of Science:
- Pulmonary Medicine
- Immunology
- Lipid Metabolism
Background:
- Airway inflammation, characterized by polymorphonuclear leukocytes (PMNs), is central to many lung diseases.
- Pulmonary alveolar macrophages (PAMs) and epithelial cells release factors that recruit inflammatory cells.
- PAMs and tracheal epithelial cells produce linoleic acid metabolites (9-HODE, 13-HODE) and arachidonic acid metabolites.
Purpose of the Study:
- To investigate the potential chemotactic activity of 9-HODE and 13-HODE on isolated PMNs.
- To compare the chemotactic potency of HODEs with known inflammatory mediators.
Main Methods:
- In vitro chemotaxis assays using isolated human and bovine PMNs.
- Dose-response analysis of 9-HODE and 13-HODE activity.
- Comparison with arachidonic acid metabolite 15-HETE and leukotriene B4 (LTB4).
Main Results:
- 9-HODE and 13-HODE demonstrated significant chemotactic activity for both human and bovine PMNs.
- The chemotactic response showed a linear dose-response relationship from 10(-10) to 10(-6) M.
- HODEs exhibited chemotactic potency comparable to 15-HETE and were approximately half as potent as LTB4 at 10(-8) M.
Conclusions:
- Linoleic acid metabolites, 9-HODE and 13-HODE, possess direct chemotactic properties for PMNs.
- These findings suggest a novel role for linoleic acid metabolism in mediating airway inflammation and PMN recruitment in lung diseases.