FATTY-ACID METABOLISM AND CELL CELL-INTERACTIONS

The majority of studies on fatty acid metabolism, not only via the lipoxygenase pathway, but also via the cyclo-oxygenase pathway, have focused on arachidonic acid. In addition, the majority of the studies have utilized the inhibitor/add-back approach, using exogenous metabolites such as the prostanoids, monohydroxy fatty acids and leukotrienes, and stimulated cells. However, we have explored the possibility that the endothelial cell lipoxygenase metabolite of linoleic acid, specifically, 13 HODE, influences adhesion of a variety of cells implicated in thrombosis, metastasis and inflammation. Albeit, we have until now only demonstrated a correlation between 13 HODE synthesis and maintaining biocompatability between vascular endothelial cells and platelets, tumor cells and leukocytes, our studies provide ample evidence that there is a common relationship between 13 HODE synthesis in vascular wall cells (both endothelial cells and smooth muscle cells), a variety of tumor cells (both human and animal) and leukocytes, and their adhesive interactions with one another. Given that the expression of adhesive sites require an alteration in the cell membrane surface, and, that intracellular 13 HODE inhibition is, in every case, associated with enhanced adhesion, we postulate the intracellular 13 HODE regulates the expression of cell surface adhesive receptors. It is also of interest to note that recent studies in the atherosclerotic-prone Watanabe rabbit are consistant with this hypothesis. Thus, Lawrence et al. [26] found that the atherosclerotic plaque in the Watanabe rabbit was less, not more, adhesive for platelets than the healthy vessel wall, and Simon et al. [27] found that the same atherosclerotic plaques had increased 15-lipoxygenase activity, consequently, an increased capacity to synthesize linoleic acid into 13 HODE. Studies presently ongoing in our laboratories are focused at identifying the mechanism (s) by which 13 HODE inhibits RGD adhesive site expression and maintains cells less reactive. © 1990 Birkhäuser Verlag.