Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization.
Bv8 and endocrine-gland-derived VEGF (EG-VEGF), or prokineticins, are two highly related, secreted proteins that we previously described as selective angiogenic mitogens. Here we describe the expression and functional characterization of Bv8 in peripheral blood cells, notably monocytes, neutrophils, and dendritic cells, and in the bone marrow. In human and mouse, the two Bv8 G protein-coupled receptors are expressed in hematopoietic stem cells and specific mature blood cells, including lymphocytes. Bv8 is highly expressed by neutrophils at sites of inflammation and can stimulate migration of monocytes, in a pertussis toxin-sensitive manner. Bv8, or EG-VEGF that shares the same receptors, increased numbers of colony-forming units granulocytic and monocytic in cultures of human or mouse hematopoietic stem cells. Systemic in vivo exposure to Bv8 or EG-VEGF resulted in significant increases in total leukocyte, neutrophil, and monocyte counts. Additionally, adenovirus (Av)Bv8 or AvEG-VEGF delivered just before 5-fluorouracil injury promoted the survival of hematopoietic cells and enhanced progenitor mobilization. In conclusion, Bv8 can promote survival and differentiation of the granulocytic and monocytic lineages. Bv8 potentially modulates growth, survival, and function of cells of the innate and adaptive immune systems, possibly through autocrine or paracrine signaling mechanisms.
LeCouter
Jennifer
J
Department of Physiology, Genentech, Inc., South San Francisco, CA 94080, USA. lecouter@gene.com
Zlot
Constance
C
Tejada
Max
M
Peale
Franklin
F
Ferrara
Napoleone
N
D002460:Cell Line; D005472:Fluorouracil / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D009479:Neuropeptides / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D005472:Fluorouracil