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Interferon‐γ and Interleukin‐4 down‐regulate soluble CD14 release in human monocytes and macrophages
Author(s) -
Landmann Regine,
Fisscher Ada E.,
Obrecht JeanPaul
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.3.323
Subject(s) - cd14 , biology , monocyte , lipopolysaccharide , cycloheximide , peripheral blood mononuclear cell , macrophage , microbiology and biotechnology , interferon gamma , cytokine , immunology , in vitro , biochemistry , flow cytometry , protein biosynthesis
CD14 is a 53‐kd glycoprotein that is mainly expressed in myeloid cells and exists in two forms. The membrane‐bound form represents the receptor for complexes of lipopolysaccharide (LPS) with LPS binding protein. The function and regulation of the soluble form are unknown. In the present study we investigated the release of soluble CD14 (sCD14) in cultures of human mononuclear leukocytes, elutriated monocytes, and monocyte‐derived macrophages. The release of sCD14 into the medium of the cells cultured for 15 and 45 h was investigated in the absence or presence of selected cytokines. sCD14 release occurred constitutively and correlated with cell number. In monocytes differentiating into macrophages, cumulative release of sCD14 was linear from day 1 to day 7. Spontaneous sCD14 release after 15 h of culture (2 × 10 6 cells/ml) was higher in the supernatant from monocytes (314 ± 58 ng/ml) than that from mononuclear leukocytes (68 ± 10 ng/ml) and similar to that from macrophages (469 ± 79 ng/ml). Cycloheximide and actinomycin D inhibited sCD14 release. Recombinant interferon‐γ (rIFN‐γ) and recombinant interleukin‐4 (rIL‐4) directly decreased sCD14 release in mononuclear leukocyte, monocyte, and macrophage cultures. rIL‐2 and rIFN‐α reduced sCD14 release into the supernatants of mononuclear leukocytes only. Use of anti‐IFN‐γ antibodies indicated that the down‐regulation of sCD14 release by rIL‐2 and rIFN‐α was partially due to induction of endogenous IFN‐γ. The down‐regulation of sCD14 release by all four cytokines was both time and dose dependent. rIFN‐γ and rIL‐4 added simultaneously had a synergistic effect on sCD14 down‐regulation. In conclusion, sCD14 release may have an immunomodulatory role in circulating monocytes, is apparently not related to the process of macrophage differentiation, and is selectively down‐regulated during an immune response when levels of IFN‐γ and IL‐4 are high.