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* Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
Division of Hematology, Immunology, and Oncology, Department of Internal Medicine II, University of Tübingen, Tübingen, Germany; and
Department of Molecular Biology, Max-Planck Institute, Martinsried, Germany
CD47, a cell surface transmembrane Ig superfamily member, is an extracellular ligand for signal regulatory protein (SIRP
). Interactions between CD47 and SIRP regulate many important immune cell functions including neutrophil (PMN) transmigration. Here we report identification of a novel function-blocking peptide, CERVIGTGWVRC, that structurally mimics an epitope on CD47 and binds to SIRP. The CERVIGTGWVRC sequence was identified by panning phage display libraries on the inhibitory CD47 mAb, C5D5. In vitro PMN migration assays demonstrated that peptide CERVIGTGWVRC specifically inhibited PMN migration across intestinal epithelial monolayers and matrix in a dose-dependent fashion. Further studies using recombinant proteins indicated that the peptide specifically blocks CD47 and SIRP binding in a dose-dependent fashion. Protein binding assays using SIRP domain-specific recombinant proteins demonstrated that this peptide directly bound to the distal-most Ig loop of SIRP, the same loop where CD47 binds. In summary, these findings support the relevance of CD47-SIRP interactions in regulation of PMN transmigration and provide structural data predicting the key residues involved on the surface of CD47. Such peptide reagents may be useful for studies on experimental models of inflammation and provide a template for the design of anti-inflammatory agents.
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