Cytokine-induced differentiation of cultured nonadherent macrophages.
Monocytes were isolated from peripheral blood and cultured in vitro for more than 3 weeks in glass chamber slides. Phenotypically and ultrastructurally these nonadherent macrophages (NAM) appear similar to connective tissue resident macrophages. They constitutively secrete a high amount of IL-1ra and little or no IL-1 alpha or IL-1 beta. When exposed to GM-CSF, IL-2, or IFN-gamma for 24 hr, NAM become adherent and undergo dramatic morphological changes. Cytokines treatment primes NAM for increased LPS-mediated TNF production and these GM-CSF- and LPS-treated NAM are cytotoxic to WEHI 164, a TNF-sensitive target. Morphological changes and TNF production are both inhibited by antimetabolites and a variety of antineoplastic drugs. Although morphology inhibition is reversible under certain circumstances, inhibition of TNF synthesis is irreversible. These findings suggest that cytokines might play a role in differentiation and maturation of long-term cultured monocytes. Furthermore, the effects of antimetabolites and antineoplastic drugs on arresting the differentiation processes may significantly impair antitumor functions of macrophages.
Tsai
V
V
Division of Rheumatology, University of California, San Diego, La Jolla 92103-8417.
Firestein
G S
GS
Arend
W
W
Zvaifler
N J
NJ
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D010587:Phagocytosis; D011458:Prostaglandins E / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007213:Indomethacin; D008727:Methotrexate