Effects of macrophage colony-stimulating factor (M-CSF) on lipopolysaccharide (LPS)-induced mediator production from monocytes in vitro.
M-CSF is a macrophage-lineage-specific growth factor that causes proliferation and differentiation of progenitor cells in the bone marrow. To investigate the effects of M-CSF on more matured cells, human monocytes were cultured in the presence or absence of M-CSF for 6 days. Addition of M-CSF at more than 10(2) U/ml resulted in higher viability and caused morphological differentiation to large macrophage-like cells. LPS-induced mediator production was also compared between M-CSF-treated and control cell. Monocytes were incubated with or without M-CSF for 3 days, and were stimulated with 1 microgram/ml of LPS for 2 days. IL-1 beta was not detected in the both culture supernatants, and PGE2 production was not influenced by M-CSF. However, amounts of G-CSF, GM-CSF, IL-6, and TNF-alpha produced in response to 1 microgram/ml of LPS were 1.5 to 2 times greater from monocytes treated with 10(4) U/ml of M-CSF than from control cells. The priming effect of M-CSF on LPS-induced cytokine production was found to require 3-day preincubation, and reached a maximum at the concentration of 10(4) U/ml. M-CSF-treated cells responded to a 10 times lower concentration of LPS than control cells in terms of cytokine production. M-CSF was also shown by flowcytometric analysis to influence the expression of CD14, a receptor for LPS, which might render monocytes more sensitive to LPS.
Asakura
E
E
Central Research Laboratory, Green Cross Corporation, Osaka, Japan.
Hanamura
T
T
Umemura
A
A
Yada
K
K
Yamauchi
T
T
Tanabe
T
T
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor