PK1/EG-VEGF induces monocyte differentiation and activation

Abstract: Macrophages exist as sentinels in innate immune response and react by expressing proin-flammatory cytokines and up-regulating antigen-presenting and costimulatory molecules. We report a novel function for prokineticin-1 (PK1)/endocrine gland-derived vascular endothelial growth factor. Screening of murine tissue sections and cells for spe-cific binding sites leads to the identification of mac-rophages as an in vivo cellular target for PK1. We demonstrate PK1 induces differentiation of murine and human bone marrow cells into the monocyte/ macrophage lineage. Human peripheral blood mono-cytes respond to PK1 by morphological changes and down-regulation of B7-1, CD14, CC chemokine receptor 5, and CXC chemokine receptor 4. Monocytes treated with PK1 have elevated inter-leukin (IL)-12 and tumor necrosis factor and down-regulated IL-10 production in response to lipopolysaccharide. PK1 induces a distinct mono-cyte-derived cell population, which is primed for release of proinflammatory cytokines that favor