In order to analyze the function of DcR3 for the regulation of cell adhesion and apoptosis in macrophages, we investigated the expression of decoy receptor 3 (DcR3) in THP-1 monocytes/macrophages. DcR3 was expressed in THP-1 and increased by phorbol 12-myristate 13-acetate (PIVIA). The formation of macrophage aggregates was observed when THP-1 cells were differentiated by PMA or stimulated with DcR3-Fc. Undifferentiated THP-1 cells were also induced to form aggregates by DcR3-Fc. The expression of integrin alpha 4 was significantly increased by DcR3-Fc. CHX-induced apoptosis in THP-1 was inhibited by DcR3-Fc, of which inhibition against CHX-induced apoptosis and aggregate formation were ameliorated by anti-VLA4 antibody. DcR3 may play a significant role in macrophages not only by a decoy receptor but also by increasing a4 integrin. (C) 2009 Elsevier Inc. All rights reserved.