Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates endothelial cell function in vitro.
We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2), thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as endothelin, were measured by radioimmunoassay after extraction from the culture supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1 alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg was similar to that observed with IVIg, indicating that the effect of IVIg was mediated by the variable region of immunoglobulin. The results suggest that part of the effects of IVIg in inflammatory vasculitis may be due to a modification of the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG antibodies may participate in the homeostatic process of endothelium under physiological conditions.
Oravec
S
S
INSERM U-430, Hôpital Broussais, Paris, France.
Ronda
N
N
Carayon
A
A
Milliez
J
J
Kazatchkine
M D
MD
Hornych
A
A
D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007231:Infant, Newborn; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D016756:Immunoglobulins, Intravenous; D013928:Thromboxane A2; D011464:Epoprostenol