Lysosome-associated membrane proteins (LAMPs), a family of highly glycosylated transmembrane proteins, are well known lysosomal markers. Recent investigations revealed the cell surface expression of LAMPs, especially after activation in various cell types. Although their role in lysosome function is under intense investigation, little is known about the function of this cell surface form of LAMPs. To investigate the role of cell surface LAMPs in macrophage activities, the human macrophage-like cell line THP-1 was stimulated with monoclonal antibodies specific to CD107a (LAMP-1) or CD107b (LAMP-2). Stimulation of CD107 enhanced LPS-induced IL-8 secretion and induced adhesion of THP-1 cells to culture plates coated with extracellular matrix proteins such as collagen, fibronectin, and laminin. Utilization of specific inhibitors of signaling adapters and Western blot analysis revealed that extracellular signal-regulated kinase (ERK) mediates the regulatory action of CD107. These results suggest that stimulation of THP-1 cells through CD107 affects macrophage-associated functions such as cytokine secretion and cellular adhesion through activation of ERK.