Eicosanoids in sickle cell disease: potential relevance of 12(s)-hydroxy-5,8,10,14-eicosatetraenoic acid to the pathophysiology of vaso-occlusion

• Published in: The Journal of laboratory and clinical medicine 1998-04, Vol.131 (4), p.344-353
• Main Authors: Setty, B.N.Yamaja, Chen, Dechun, O'Neal, Pat, Littrell, James B., Grossman, Mark H., Stuart, Marie J.
• Format: Article
• Language: English
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - blood; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - physiology; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - urine; Adolescent; Adult; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - physiopathology; Anemia, Sickle Cell - urine; Anemias. Hemoglobinopathies; Animals; Arterial Occlusive Diseases - blood; Arterial Occlusive Diseases - physiopathology; Arterial Occlusive Diseases - urine; Biological and medical sciences; Cattle; Cell Adhesion; Child; Child, Preschool; Diseases of red blood cells; Endothelium, Vascular - pathology; Gene Expression Regulation - physiology; Hematologic and hematopoietic diseases; Humans; Medical sciences; Middle Aged; P-Selectin - blood; RNA, Messenger - genetics; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 0022-2143; 1931-5244; 1532-6543; 1878-1810
• DOI: 10.1016/S0022-2143(98)90185-8

The monohydroxyeicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), which is derived from oxygenation of arachidonic acid by 12-lipoxygenase, is one of the major metabolites in platelets. In a recent study, we have showed that this eicosanoid stimulated basal sickle-red-cell-endothelial-cell adhesion. To understand the pathophysiologic significance of 12-HETE, we measured the levels of this eicosanoid in plasma and urine from children with sickle cell disease. We found that as compared with controls, plasma 12-HETE levels are increased in patients with sickle-cell disease in the steady state, and are increased further during vaso-occlusive crises. Urinary 12-HETE levels were also increased during the steady state. We also assessed plasma levels of soluble P-selectin (another potential marker for platelet activation), and found changes in the levels of this marker similar to those seen with plasma 12-HETE. In additional studies, we found that 12-HETE enhanced hypoxia-induced sickle-red-cell—endothelial adherence, and that this effect was mediated by potentiation of agonist-induced upregulation of the expression of the mRNA for vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. Because 12-HETE appears to enhance both basal and agonist-induced sickle-red-cell adhesion, this metabolite could potentially play a role in the pathogenesis of the vaso-occlusive crisis (VOC) in sickle-cell disease.