Participation of leptin in the determination of the macrophage phenotype: an additional role in adipocyte and macrophage crosstalk

Abstract

Macrophages develop into specialized cell types with special functional properties, depending on locally produced stimuli. Adipose tissue macrophages present particular characteristics, such as the M2 cell phenotype, and produce cytokines and chemokines usually produced by M1 cells. Our aim was to study the role of leptin, which is an adipokine produced and released by adipocytes, in the induction of these characteristics in macrophages found in the adipose tissue. Human CD14(+) cells were obtained and maintained in culture with IFN-γ (classical M1 phenotype), IL-4 (alternative M2 phenotype) or leptin for 5 d. Surface marker expression was then analyzed by cytometry. In addition, the release of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-10, IL-1ra, MCP-1, MIP-1α, and RANTES was quantified by ELISA after an LPS stimulus, in the culture supernatant. Macrophages exposed to leptin in culture expressed surface markers that were more similar to the M2 phenotype, but they were able to produce TNF-α, IL-6, IL-1β, IL-1ra, IL-10, MCP-1, and MIP-1α, as observed for M1 cells. Results suggest that leptin strongly contributes to the phenotype observed in macrophages found in adipose tissue.