Intravenously administered macrophage colony-stimulating factor (M-CSF) specifically acts on the spleen, resulting in the increasing and activating spleen macrophages for cytokine production in mice

• Published in: Immunopharmacology Vol. 37; no. 1; pp. 7 - 14
• Main Authors: Asakura, Eiji, Yamauchi, Takeshi, Umemura, Akio, Hanamura, Takuji, Tanabe, Toshizumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.1997
• Subjects: Animals; Cells, Cultured; CHO Cells - metabolism; Cricetinae; Hematopoiesis; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; IL-6; Injections, Intravenous; Interleukin-6 - biosynthesis; Lipopolysaccharides - pharmacology; LPS; M-CSF; Macrophage Activation - drug effects; Macrophage Colony-Stimulating Factor - pharmacokinetics; Macrophage Colony-Stimulating Factor - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred Strains; Priming; Spleen - cytology; Spleen - drug effects; Spleen macrophage; Tissue Distribution; M-CSF, macrophage-colony-stimulating factor; IFN-γ, interferon-γ; CFU-M, -GM, colony forming unit-macrophage, -granulocyte-macrophage; M-CSF; TNF, tumor necrosis factor; Priming; HSA, human serum albumin; ELISA, enzyme-linked immunosorbent assay; LPS; IL-6; G-, GM-CSF, granulocyte-, granulocyte-macrophage-CSF; Hematopoiesis; IL-6, interleukin-6; Spleen macrophage; LPS, lipopolysaccharide; FCS, fetal calf serum
• DOI: 10.1016/S0162-3109(96)00165-8
• ISSN: 0162-3109

IL-6 was transiently expressed in sera of mice after a bolus intravenous injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF at 250 μg/kg/day for 5 days prior to an injection of 25 μg/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor cells 7-fold when injected intravenously. Spleen macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS-stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously administered M-CSF was detected at higher concentration and for longer duration in the spleen than in any other organs examined. Spleen macrophages incubated in-vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced IL-6 than untreated cells. These results indicate that intravenously administered M-CSF not only enhances macrophage development in the spleen, but also primes mature macrophages for cytokine production.