THE INFLUENCE OF APOPTOTIC NEUTROPHILS ON PRODUCTION OF CYTOKINES AND PROSTAGLANDIN E2 BY HUMAN M1 MACROPHAGES
Engulfment of apoptotic cells by monocytes and unprimed (naive) macrophages is known to down-regulate pro-inflammatory and up-regulate anti-inflammatory cytokines evidencing M2 polarization. In the current study, we investigated whether apoptotic cells influence human M1 macrophages generated in the presence of GM-CSF. The data obtained demonstrate that following pre-incubation with apoptotic neutrophils M1 macrophages significantly decrease their capacity to stimulate proliferation of allergenic T-cells thus adopting M2 features. The multi-plex analysis of 27 cytokines using fluorescent bead-based assay demonstrated a inhibitory effect of apoptotic cells on production of both pro- (TNF-α, IL-6, IL-1β) and anti-inflammatory (IL-10, IL1-ra) cytokines, as well as a secretion of immunoregulatory cytokines (IL-2, IFN-γ, IL-12, IL-4, IL-9, IL-13, IL-15, IL-17), growth factors (G-CSF, GM-CSF, IL-7, FGF-basic, PDGF, VEGF), and chemokines (IL-8, IP-10, MCP-1, Rantes, Eotaxin). While suppressing most cytokines, apoptotic neutrophils have a bidirectional effect on the synthesis of PGE2, enhancing its production in 7 cases (subgroup 1), and suppressing PGE2 production in 6 cases (subgroup 2). The stronger suppressor effect of apoptotic cells on production of IL-6, IL-17, FGF-basic, and VEGF is detected in subgroup 2, which is characterized by a higher level of PGE2 in intact macrophages and its pronounced decrease after contact with apoptotic cells. These results show that M1 macrophages are influenced by apoptotic neutrophils that exert a unidirectional suppressor effect on the production of various cytokines, including anti-inflammatory cytokines, growth factors and chemokines, but have a bidirectional effect on the synthesis of PGE2.
About the authorsChernykh E.R.
Ostanin Alexandr A.
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