Involvement of pattern recognition receptors in the induction of cytokines and reactive oxygen intermediates production by human monocytes/macrophages stimulated with tumour cells

Abstract

Background: Some ligands of pattern recognitionm receptors (PRR) are present on tumour cells. The role of PRR in signalling for cytokine and reactive oxygen intermediates (ROI) production by monocytes and monocyte-derived macrophages (MDM) stimulated with tumour cells was studied. Materials and Methods: Monocytes/MDM were pretreated with PRR ligands or anti-PRR monoclonal antibodies (mAbs) and stimulated with tumour cells. Cytokine secretion was measured by enzyme-linked immunoassay (ELISA) and ROI production by luminol-dependent chemiluminescence (CL). Results: The ligands of scavenger receptor A (SR-A): (fucoidan, polyguanylic acid (polyG) and modified low density lipoproteins (LDL)) and B (SR-B) (native and modified LDL, phosphatidylserine (PdS)) and of mannose receptor (MR) (mannan), induced tumour necrosis factor alpha (TNF) and ROI (except LDL) release by monocytes. Production of TNF and interleukin-10 (IL-10) by MDM was stimulated by SR-A ligands and mannan. Tumour cell-induced TNF and IL-10 production by monocytes, but not MDM, was diminished by fucoidan and polyG, while ROI release was reduced by MR and SR-A ligands. Supplementation of tumour cells with modified LDL and PdS enhanced their stimulatory capacity. TNF and ROI release by tumour cells-stimulated monocytes was inhibited by anti-CD36 and anti-MR (clone PAM-1) mAbs. Conclusion: SR and MR may be involved to different extents in the induction of cytokines and ROI production by monocytes, but not MDM, stimulated with tumour cells

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