Binding of 13-HODE and 5-, 12- and 15-HETE to endothelial cells and subsequent platelet, neutrophil and tumor cell adhesion.

Some studies report that endothelial cells preferentially take up the lipoxygenase-derived arachidonic acid metabolite, 5-hydroxyeicosatetraenoic acid (5-HETE), released from stimulated leukocytes (polymorphonuclear leukocytes, PMNs), whereas others report that endothelial cells preferentially take up 12-HETE released from platelets. The biological relevance of these observations, however, is unknown. Recently, we and others have found that, under basal conditions, endothelial cells, PMNs and tumor cells metabolize linoleic acid via the lipoxygenase enzyme to 13-hydroxyoctadecadienoic acid (13-HODE). We propose that endogenous levels of these metabolites regulate blood-vessel wall cell adhesion. In this study, we have measured (1) the relative binding of 5-, 12- and 15-HETE, and 13-HODE to endothelial cell monolayers, and (2) their effects on endothelial cell adhesivity with platelets, PMNs and tumor cells. There was a dose-related and specific binding of 5-[3H]HETE to endothelial cells but no binding of 12- or 15-HETE or 13-HODE. Platelet or PMN adhesion to endothelial cells was unaffected by the 5-HETE binding, but tumor cell adhesion was blocked by 40% (P less than 0.01). Interestingly, preincubation of endothelial cells with 13-HODE, 12-HETE or 15-HETE decreased platelet adhesion to endothelial cells (P less than 0.05), even though these metabolites did not bind to the endothelial cells. We conclude that 5-HETE preferentially binds to endothelial cells and interferes with a specific receptor for tumor cells, whereas the other metabolites neither bind to cells nor affect cell adhesion.
AuthorsT A Haas, E Bastida, K Nakamura, F Hullin, L Admirall, M R Buchanan
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 961 Issue 2 Pg. 153-9 (Jul 22 1988) ISSN: 0006-3002 [Print] NETHERLANDS
PMID3390452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hydroxyeicosatetraenoic Acids
  • Linoleic Acids
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • 13-hydroxy-9,11-octadecadienoic acid
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Cell Adhesion (drug effects)
  • Endothelium, Vascular (metabolism)
  • Humans
  • Hydroxyeicosatetraenoic Acids (metabolism)
  • Linoleic Acids (metabolism)
  • Neoplasms (pathology)
  • Neutrophils (cytology)
  • Platelet Adhesiveness (drug effects)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: