Platelet-derived growth factor (PDGF) activates primitive hematopoietic precursors (pre-CFCmulti) by up-regulating IL-1 in PDGF receptor-expressing macrophages.
Platelet-derived growth factor (PDGF-BB) is known to stimulate growth of fibroblasts and smooth muscle cells via interaction with specific PDGF-B receptors on their surfaces. Hematopoietic precursor cells are not known to respond directly to PDGF, and PDGF receptors have never been reported on normal hematopoietic cells. We report a consistent stimulatory effect of PDGF-B on primitive pluripotential hematopoietic cells (pre-CFCmulti) in suspension cultures of mouse bone marrow that resembles effects obtainable previously only with IL-1. Further, we show that the effect depends on plastic-adherent accessory cells and is abrogated by neutralizing antibodies to IL-1 beta, that PDGF strongly up-regulates IL-1 mRNA levels in marrow macrophages but not in marrow fibroblast lines, and finally provide a first report of expression of RNA transcripts for PDGF-B receptors in normal marrow macrophages. Together, the results suggest the existence of a novel cytokine loop implicating monocyte/macrophages as cells reactive to PDGF and highlighting IL-1 induction as a significant feature of their PDGF response.
Yan
X Q
XQ
Ontario Cancer Institute, Toronto, Canada.
Brady
G
G
Iscove
N N
NN
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000502:physiology; D001483:Base Sequence; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D013535:Suspensions; D015854:Up-Regulation
D000906:Antibodies; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013535:Suspensions; D017479:Receptors, Platelet-Derived Growth Factor