EMR2/CD312 is a member of the adhesion-GPCR family that contains extracellular EGF-like domains. Previously it has been shown to interact with chondroitin sulphate glycosatninoglycans in an isoform-specific manner. Although EMR2 expression has been found to be restricted to human myeloid cells, its expression profile has not yet been systemically characterized. In this report, we show that EMR2 receptor expression is up-regulated during differentiation and maturation of macrophages, and is conversely down-regulated during dendritic cell maturation. We also demonstrate that EMR2 receptor alternative splicing and glycosylation is regulated during myeloid differentiation. In monocytes and macrophages, EMR2 can be specifically up-regulated by LPS and IL-10 via an IL-10-mediated pathway. In inflamed tissues, EMR2 is detected in subpopulations of myeloid cells including macrophages and neutrophils. The results presented here further support the idea that EMR2 plays a role in the migration and adhesion of myeloid cells during cell differentiation, maturation, and activation. (c) 2006 Elsevier Inc. All rights reserved.