MONONUCLEAR CELL-CONDITIONED MEDIUM ENHANCES THROMBIN-STIMULATED PGI(2) PRODUCTION BY HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN CULTURE

We investigated the effect of blood mononuclear cell-conditioned mediu m on prostacyclin (PGI(2)) production by human umbilical vein endothel ial cells in culture (HUVEC), and compared the potency of the conditio ned medium in PGI(2) production with that of various cytokines and lip opolysaccharide (LPS). HUVEC which had been preincubated with LPS, int erleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor (TNF a lpha), or interferon-gamma (IFN-gamma) produced more PGI(2) than contr ol cells in response to thrombin. However, the HUVEC preincubated with the conditioned medium made with mononuclear cells with or without LP S (LPS-Mo-CM, Mo-CM) produced more PGI(2) than those preincubated with LPS, IL-1 alpha, IL-1 beta, TNF alpha, or IFN-gamma. Although the con centrations or IL-1 beta and TNF alpha in the post-culture medium of H UVEC treated with LPS-Mo-CM were much higher than those with Mo-CM, LP S-Mo-CM which was made with 13 000/ml of mononuclear cells and 1 mu g/ ml of LPS did not significantly augment the subsequent PGI(2) producti on by HUVEC as compared with Mo-CM made with the same numbers of monon uclear cells. PGI(2) production by Mo-CM-treated HUVEC still exceeded that of control cells, even when an excess amount of antibody to TNF a lpha and/or IL-1 alpha was added to the Mo-CM. It is possible that Mo- CM contains unknown cytokines besides IL-1 and TNF which stimulate the HUVEC to produce PGI(2).