A novel anti-apoptosis serum factor that down-regulates fas-mediated apoptosis.

Abstract

The Fas antigen (CD95) is a receptor for apoptotic cell death signals. Human T Jurkat cells that express the Fas molecule on the cell surface are sensitive to cytotoxic anti-Fas monoclonal antibodies (mAbs). We report here that fetal calf serum (FCS) contains a novel factor (SAF: Serum Anti-Apoptosis Factor) that suppresses Fas-mediated apoptosis of Jurkat cells. The apoptotic cell death of Jurkat cells induced by an anti-Fas mAb was accelerated when FCS was removed from the medium. Depletion of serum itself did not induce apoptosis without the mAb. The apoptosis-suppressing activity was not seen in neonatal calf or adult bovine serum, suggesting that the SAF activity was developmentally regulated. The anti-apoptosis activity was not detected in any fraction of FCS obtained on gel filtration chromatography. However, the activity was recovered in a certain fraction on the addition of calf serum, suggesting that the anti-apoptotic activity of SAF requires other serum factor(s). We purified SAF from FCS using an assay system reconstituted with calf serum, and raised antibodies (Abs) to it in rabbits. The anti-SAF Ab inhibited the apoptosis-suppressing activity, indicating that SAF is a key factor for the anti-apoptotic activity of FCS.