In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 58, No. 3 ( 1995-09-01), p. 351-358
Abstract:
Interleukin-10 (IL-10), a cytokine produced by type 2 belper T (Th2) cells, inhibits the microbicidal effector function of interferon-γ (EFN-γ)-activated macrophages. However, recent observations indicate that IL-10, like IFN-γ, increases FcγRI expression and FcγR-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of EL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (FcγR-mediated ingestion) or with C3b/C3bi fragments of the complement system (GR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations ≥1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-EL-10 monoclonal antibody (mAb). As previously reported, ILIO stimulated FcγRI expression on monocytes but did not induce the expression of FcγRII, FcγRIII, CR1, and CR3. IFN-γ, like EL-10, up-regulated only FcγRI expression but significantly reduced both FcγR- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-γ-induced inhibition of both FcγR- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three FcγRs and also inhibited FcγR-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on FcγR expression but also completely reversed the IL-4-induced suppression of FcγR-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-EL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes. These results demonstrate that IL-10 is a potent up-regulator of the phagocytic activity of human mononuclear phagocytes and indicate that this function may be in sensitive balance with the relative concentrations of EL-10, IL-4, and IFN-γ.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1002/jlb.58.3.351
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
1995
detail.hit.zdb_id:
2026833-6
SSG:
12
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