Abstract
Monocyte-derived macrophage (MΦ) subsets are generated by antagonistic induction pathways. A helper MΦ-type (Mh-MΦ) is induced by interferon gamma (IFN-γ), whereas a cytotoxic MΦ-type (Mc-MΦ), induced by interleukin-10 (IL-10), is a potent mediator of antibody-dependent cellular cytotoxicity (ADCC). Compared with MΦ from healthy adults [peripheral blood monocyte-derived macrophages (PBMΦ)], cord blood MΦ (CBMΦ) were found less capable of generating Mh-MΦ. Here we tested the hypothesis that their generation of Mc-MΦ via IL-10 is also impaired. MΦ surface markers were phenotyped. IL-10 protein and mRNA production were detected after stimulation [αCD3 monoclonal antibody (mAb)]. CBMΦ or PBMΦ were co-cultured with MΦ-depleted mononuclear cells of adults and CD4-targeting antibodies as models for ADCC were added. In cord blood, we found diminished αCD3-induced IL-10 protein and mRNA production (p < 0.05 versus adults). Basal CD16 and HLA-DR expressions on CBMΦ of preterm and full-term neonates were lower (p < 0.05 versus PBMΦ). IL-10 had reduced effects on CD16 up- and HLA-DR down-modulation on CBMΦ (p < 0.05 versus PBMΦ). CD4-directed receptor modulation and deletion were reduced in the presence of CBMΦ (p < 0.05 versus PBMΦ). IL-10 failed to enhance their ADCC capacity, which was in contrast to PBMΦ (p < 0.05). These data suggest that CBMΦ have an impaired cytotoxic capacity via lower sensitivity toward IL-10.
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Abbreviations
- ADCC:
-
antibody-dependent cellular toxicity
- αCD4:
-
mAb anti-CD4 monoclonal antibody
- CBMΦ:
-
cord blood monocyte-derived macrophages
- CBMNCs:
-
cord blood mononuclear cells
- gp120:
-
HIV glycoprotein 120
- IFN-γ:
-
interferon gamma
- MΦ:
-
monocyte-derived macrophages
- PBMΦ:
-
peripheral blood monocyte-derived macrophages
- PBMNCs:
-
peripheral bloodmononuclear cells
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Gille, C., Spring, B., Tewes, L. et al. Diminished Response to Interleukin-10 and Reduced Antibody-Dependent Cellular Cytotoxicity of Cord Blood Monocyte-Derived Macrophages. Pediatr Res 60, 152–157 (2006). https://doi.org/10.1203/01.pdr.0000228345.58509.7b
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DOI: https://doi.org/10.1203/01.pdr.0000228345.58509.7b
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