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Phagocytosis of primary human macrophages is elevated by ex vivo supplementation with n-3 PUFA

Kirchhoff, R.; Chromik, M. A.; Schebb, N. H.

2025-08-02 immunology
10.1101/2025.07.30.667640 bioRxiv
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ScopeEpidemiologic studies show that a high n-3 polyunsaturated fatty acid (PUFA) status is beneficial for health and inflammatory diseases. However, results of nutrition studies investigating the impact of n-3 PUFA intake on immune functions, such as phagocytosis, are contradictory. In order to gain more insights into the role of n-3 PUFAs on phagocytosis, we investigated the modulation of phagocytosis by n-3 PUFAs and derived oxylipins in human macrophages. Methods and resultsUsing an established ex vivo supplementation strategy, primary human macrophages were supplemented with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The PUFA pattern of the cells was shifted from a low n-3 PUFA status towards a high n-3 PUFA status. This was accompanied by a shift in the oxylipin pattern, reduced pro-inflammatory prostaglandin levels, increased phagocytosis in the supplemented macrophages, and reduced inhibitory effect of PGE2 on phagocytosis. However, when tested alone, n-3 PUFA derived oxylipins did not impact phagocytosis. ConclusionUnder controlled conditions, an increased n-3 PUFA status of macrophages resulted in an elevation of phagocytosis. Less formation of prostaglandins could contribute to this effect, whereas n-3 PUFA derived oxylipins, particularly multihydroxy PUFAs, appear to have a limited impact on phagocytosis following n-3 PUFA supplementation.

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