Polyunsaturated fatty acid metabolism in human Mono Mac‐1 cells

Abstract

The human monocyte‐like Mono Mac‐1 (MM‐1) cell line is a good model to study the differentiation of monocytes toward a macrophage‐like phenotype. In this study, polyunsaturated fatty acid (PUFA) metabolism in untreated and LPS‐differentiated MM‐1 cells was investigated. When MM‐1 cells were incubated with various n‐3 and n‐6 PUFA, they were efficiently elongated and desaturated through the delta‐6 and delta‐5 desaturase steps with some capacity to convert 22:4n‐6 and 22:5n‐3 to 22:5n‐6 and 22:6n‐3, respectively. The cells could also retroconvert 22:4n‐6 and 22:5n‐3 to 20:4n‐6 and 20:5 n‐3, respectively. When cells were differentiated to a macrophage phenotype, they were more enriched in 20:4n‐6 and 20:5n‐3. Additionally, differentiated cells accumulated 2‐fold more 20:4n‐6 and 6‐fold more 20:5n‐3 compared to undifferentiated cells when incubated with their 18‐carbon precursors. Similarly, retroconversion to 20:4n‐6 and 20:5n‐3 from their 22‐carbon counterparts was also more efficient in differentiated cells. Since 20:4n‐6 and 20:5n‐3 are substrates for the 5‐lipoxygenase (5‐LO), its expression was also investigated. 5‐LO mRNA was increased 10‐fold following differentiation as determined by qPCR, and protein content increased from undetectable levels as assessed by Western blots. Differentiated cells also acquired the capacity to synthesize leukotriene B4 following ionophore stimulation. In conclusion, PUFA metabolism of MM‐1 cells is modified following differentiation and these cells may represent a good model to investigate changes in PUFA and eicosanoid metabolism that accompany human monocyte‐macrophage differentiation. (Supported by the Canadian Institutes of Health Research and the Canada Research Chairs).