Induction of Apoptosis by a Secreted Lipocalin That is Transcriptionally Regulated by IL-3 Deprivation

Abstract

Many hematopoietic cells undergo apoptosis when deprived of specific cytokines, and this process requires de novo RNA/protein synthesis. Using DNA microarrays to analyze interleukin-3 (IL-3)–dependent murine FL5.12 pro–B cells, we found that the gene undergoing maximal transcriptional induction after cytokine withdrawal is 24p3 , which encodes a secreted lipocalin. Conditioned medium from IL-3–deprived FL5.12 cells contained 24p3 and induced apoptosis in naı̈ve FL5.12 cells even when IL-3 was present. 24p3 also induced apoptosis in a wide variety of leukocytes but not other cell types. Apoptotic sensitivity correlated with the presence of a putative 24p3 cell surface receptor. We conclude that IL-3 deprivation activates 24p3 transcription, leading to synthesis and secretion of 24p3, which induces apoptosis through an autocrine pathway.