Induction of apoptosis by a secreted lipocatin that is transcriptionally regulated by IL-3 deprivation

Many hematopoietic cells undergo apoptosis when deprived of specific cytoki nes, and this process requires de novo RNA/protein synthesis. Using DNA mic roarrays to analyze interleukin-3 (IL-3)- dependent murine FL5.12 pro-B cel ls, we found that the gene undergoing maximal transcriptional induction aft er cytokine withdrawal is 24p3, which encodes a secreted lipocalin. Conditi oned medium from IL-3-deprived FL5.12 cells contained 24p3 and induced apop tosis in naive FL5.12 cells even when IL-3 was present. 24p3 also induced a poptosis in a wide variety of leukocytes but not other cell types. Apoptoti c sensitivity correlated with the presence of a putative 24p3 cell surface receptor. We conclude that IL-3 deprivation activates 24p3 transcription, l eading to synthesis and secretion of 24p3, which induces apoptosis through an autocrine pathway.