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Suppression of the reactive oxygen intermediates production of human macrophages by colorectal adenocarcinoma cell lines
Author(s) -
Siegert A.,
Denkert C.,
Leclere A.,
Hauptmann S.
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00915.x
Subject(s) - macrophage , cell culture , cytotoxicity , cytotoxic t cell , in vivo , in vitro , cytokine , biology , cell , cancer research , microbiology and biotechnology , cell growth , transforming growth factor , immunology , biochemistry , genetics
Summary Although some in vitro studies indicate that macrophages exert cytotoxic responses against tumour cells by production of reactive oxygen intermediates (ROI), no obvious impairment of tumour cell growth is visible in various human malignant tumours, which contain a large number of tumour‐associated macrophages (TAM). We made use of an in vivo ‐like co‐culture model of multicellular tumour spheroids of three colon carcinoma cell lines (HRT‐18, HT‐29, CX‐2) and three functionally different phenotypes of human macrophages (27E10, RM3/1, 25F9) to investigate if tumour cells deactivate macrophage cytotoxicity. The production of ROI was measured by a lucigenin‐amplified chemiluminescence assay in a 96‐well‐microplate luminometer. Different capabilities to produce ROI by different macrophage phenotypes were observed. However, independent of the macrophage phenotype and the tumour cell type a significant inhibition of ROI formation was found in co‐cultures after 1 hr, 1 and 2 days. Macrophages were also suppressed by tumour cell supernatants, which contained anti‐inflammatory cytokines transforming growth factor‐β1 (TGF‐β1) and negligible levels of interleukin‐4 (IL‐4) and IL‐10 as shown by enzyme‐linked immunosorbent assay (ELISA). Although recombinant human cytokines TGF‐β1, IL‐10 and IL‐4 inhibited the production of ROI in freshly isolated monocytes, these cytokines had no effect on differentiated macrophage phenotypes, indicating that these cytokines are not involved in mediating tumour‐induced suppression of ROI production by human macrophages.