Stimulation of human monocytes via CD45, CD44, and LFA-3 triggers macrophage-colony-stimulating factor production. Synergism with lipopolysaccharide and IL-1 beta.
Stimulation of human monocytes with immobilized mAb directed against the CD45, CD44, or LFA-3 Ag induced the production of macrophage-CSF (M-CSF). M-CSF-specific transcripts appeared at 3 h poststimulation, were further increased by 12 h, and were still detectable at 24 h. M-CSF gene expression was accompanied by the induction of small but detectable amounts of M-CSF protein. LPS and IL-1 beta, but not IL-6 or TNF-alpha, dramatically augmented the ability of anti-CD45, anti-CD44, and anti-LFA-3 antibodies to induce M-CSF secretion but failed to stimulate M-CSF secretion in the absence of antibody. M-CSF activity in the culture supernatants was first detectable at 8 h of culture, peaked at day 2, and declined thereafter. Purified F(ab)2 fragments of anti-CD45 antibody were also effective in inducing M-CSF message and secretion, indicating that the Fc gamma RII is not involved in this response. Stimulation of cells with antibodies to the monocyte surface Ag MAC-1, LFA-1, and ICAM-1 did not result in M-CSF secretion. Moreover, LPS and IL-1 beta failed to synergize with these Ag in inducing M-CSF production. Together, these results indicate that stimulation of monocytes via the cell surface Ag CD45, CD44, and LFA-3 can trigger M-CSF production. However, second signals that can be provided by IL-1 beta or LPS are required to regulate optimal M-CSF protein secretion.
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
M F
MF
Gruber
D S
DS
Webb
T L
TL
Gerrard
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D018968:CD58 Antigens; D002478:Cells, Cultured; D004357:Drug Synergism; D006649:Histocompatibility Antigens / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D018968:CD58 Antigens; D006649:Histocompatibility Antigens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D016173:Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens