Signal regulatory protein (SIRP) alpha, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRP alpha and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. Here, we consider an alternative way to interrupt the interaction between CD47 and SIRP alpha. We expressed the extracellular domains of the human SIRP alpha (hSIRP(ext)) and the human CD47 (hCD47(ext)) in Escherichia coli as Trx fusion proteins, and purified them by using affinity chromatography. We show that the purified fusion protein Trx-SIRPext could interact in vitro with Trx-hCD47(ext). Moreover, Trx-SIRPext could effectively bind to Jurkat T-ALL cells, which expressed CD47 at a high level. CD47(ext), on the other hand, bound to human macrophages. In vitro phagocytosis assay showed that these fusion proteins could enhance the phagocytosis of Jurkat cells by macrophage, with Trx-hSIRP(ext) showed a higher efficiency than Trx-CD47(ext). These results indicated that the soluble Trx-hSIRP(ext) and Trx-CD47(ext) polypeptides could be alternative molecules to interrupt CD47-SIRP alpha interaction between leukemia cells and macrophages, and might be potentially useful for the targeted therapy of leukemia. (c) 2012 Elsevier Inc. All rights reserved.