Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium.
Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin.
Dudley
D J
DJ
Department of Obstetrics and Gynecology, University of Utah, Salt Lake City.
Mitchell
M D
MD
Branch
D W
DW
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000906:Antibodies / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D010743:Phospholipids / Q000276:immunology*; D011453:Prostaglandins / Q000276:immunology / Q000502:physiology
D000906:Antibodies; D010743:Phospholipids; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol