Interleukin 1 and poly(rI).poly(rC) induce production of granulocyte CSF, macrophage CSF, and granulocyte-macrophage CSF by human endothelial cells.
Electrophoretically pure human interleukin 1 (IL-1) beta was found to stimulate human endothelial cells in monolayer culture to elaborate colony-stimulating activity (CSA). Supernatant fluids from cultures stimulated with increasing concentrations of IL-1 were found to stimulate colony formation of myeloid (CFU-GM), erythroid (BFU-E), and multipotent (CFU-GEMM) progenitor cells in a dose-dependent fashion. The effect on mixed colony formation, however, was less than on CFU-GM and BFU-E growth. Similar to IL-1, the double-stranded RNA polyriboinosinic-polyribocytidilic acid (poly[rI].poly[rC]) also stimulated release of CSA by endothelial cells in a dose-dependent manner. The kinetics of IL-1-induced CSA release as opposed to poly(rI).poly(rC)-induced release were found to be different, in that poly(rI).poly(rC)-induced CSA production occurred more slowly. An anti-IL-1 beta antiserum was able to completely neutralize the IL-1-induced CSA release, but had no effect on poly(rI).poly(rC)-dependent CSA production, indicating that the latter effect was mediated by other mechanisms than intermediate production of IL-1 beta. Using specific immunologic assays, IL-1- as well as poly(rI).poly(rC)-inducible production of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF, and macrophage CSF was found. The release of CSF from endothelial cells in response to IL-1 may be a mechanism for stimulating production of neutrophils and mononuclear phagocytes, and for attracting and activating these cells at sites of inflammation.
Fibbe
W E
WE
Department of Hematology, University Medical Center, Leiden, The Netherlands.
Daha
M R
MR
Hiemstra
P S
PS
Duinkerken
N
N
Lurvink
E
E
Ralph
P
P
Altrock
B W
BW
Kaushansky
K
K
Willemze
R
R
Falkenburg
J H
JH
D001853:Bone Marrow; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages; D011070:Poly I-C / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011070:Poly I-C