PK1/EG-VEGF induces monocyte differentiation and activation.
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 site 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 alpha 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.
Dorsch
Marion
M
Millennium Pharmaceuticals Inc., 35 Landsdowne St., Cambridge, MA 02139, USA.
Qiu
Yubin
Y
Soler
Dulce
D
Frank
Nita
N
Duong
Thao
T
Goodearl
Andrew
A
O'Neil
Steve
S
Lora
Jose
J
Fraser
Christopher C
CC
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D018417:Th1 Cells / Q000502:physiology; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000378:metabolism / Q000494:pharmacology*
D018122:B7-1 Antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived