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Published online before print May 20, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0205061

Received for publication February 1, 2005.
Revised April 19, 2005.
Accepted for publication April 26, 2005.

Article

PK1/EG-VEGF induces monocyte differentiation and activation

Millennium Pharmaceuticals Inc., Cambridge, Massachusetts

^@ To whom correspondence should be addressed. E-mail: fraser{at}mpi.com.

	Abstract

Macrophages exist as sentinels in innate immune response and react by expressing proinflammatory 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 specific binding sites leads to the identification of macrophages 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 monocytes 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 interleukin (IL)-12 and tumor necrosis factor and down-regulated IL-10 production in response to lipopolysaccharide. PK1 induces a distinct monocyte-derived cell population, which is primed for release of proinflammatory cytokines that favor a T helper cell type 1 response.

Key Words: macrophage • innate • Th1 • cytokine

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