Monocytes stimulate expression of the Bcl-2 family member, A1, in endothelial cells and confer protection against apoptosis

We have investigated the molecular mechanisms underlying the ability of per ipheral blood monocytes to block apoptosis induction in endothelial cells. Monocytes stimulated the expression of the bcl-2 homologue A1 in serum-star ved endothelial cells after 6 h of coincubation, with elevated A1 levels pe rsisting for up to 21 h, IL-1 and TNF also stimulated A1 expression at 6 h, but A1 transcript levels fell by 21 h, Direct cellular contact with monocy tes was required for stimulation of A1 mRNA in endothelial cells. Stimulati on of endothelial cell A1 mRNA by monocytes was not inhibited by anti-beta( 2) integrin Abs, but anti-platelet endothelial cell adhesion molecule-1 (PE CAM-1) mAb reduced A1 transcript levels at 21 h, Studies employing either T NF on its own, or anti-TNF in endothelium/monocyte cocultures showed that T NF plays a role in the early (6-h) stimulation of A1, but is less important for the sustained elevation of A1 levels at 21 h. Serum-starved endothelia l cells demonstrated increased survival and decreased apoptosis after cocul ture with monocytes. IL-10 reduced A1 mRNA expression in, as well as surviv al of, endothelial cells that were cocultured with monocytes, In comparison with A1, Bcl-2 was expressed at low levels and was up-regulated by monocyt es only at 21 h, while neither Bax nor Bcl-x(L) levels were altered by mono cytes. The interaction of monocytes with endothelium during the course of a n inflammatory reaction may provide survival signals to endothelial cells.