Abstract
Recently it was discovered that tissue-resident macrophages derive from embryonic precursors, not only from peripheral blood monocytes, and maintain themselves by self-renewal. Most in-vitro studies on macrophage biology make use of in-vitro cultured human monocyte-derived macrophages. Phagocytosis of IgG-opsonized particles by tissue-resident macrophages takes place via interaction with IgG receptors, the Fc-gamma receptors (FcγRs). We investigated the FcγR expression on macrophages both in-vivo and ex-vivo from different human tissues. Upon isolation of primary human macrophages from bone marrow, spleen, liver and lung, we observed that macrophages from all studied tissues expressed high levels of FcγRIII, which was in direct contrast with the low expression on blood monocyte-derived macrophages. Expression levels of FcγRI were highly variable, with bone marrow macrophages showing the lowest and alveolar macrophages the highest expression. Kupffer cells in the liver were the only tissue-resident macrophages that expressed the inhibitory IgG receptor, FcγRIIB. This inhibitory receptor was also found to be expressed by sinusoidal endothelial cells in the liver. In sum, our immunofluorescence data combined with ex-vivo stainings of isolated macrophages indicated that tissue-resident macrophages are remarkably unique and different from monocyte-derived macrophages in their phenotypic expression of IgG receptors. Tissue macrophages show distinct tissue-specific FcγR expression patterns.
Highlights
Since the 1960s the dogma has been that the homeostasis of tissue-resident macrophages relies on the constant recruitment of blood monocytes [1]
A subpopulation of about 10% of the blood monocytes is known to express FcγRIIIA (CD16). These CD16pos cells are believed to represent a specific subset of monocytes with a more mature phenotype than the CD16neg monocytes [23,24]. Reasoning that these specific circulating monocytes could be a source of a fraction of the tissue-resident macrophages, we investigated whether these cells showed a different phenotype upon the standard nine days of culturing in either granulocyte macrophage-colony stimulating factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF)
Parabiotic and adoptive-transplant studies in rodents have shown that tissue-resident macrophages are derived from embryonic precursors and maintain themselves by self-renewal [6,16]
Summary
Since the 1960s the dogma has been that the homeostasis of tissue-resident macrophages relies on the constant recruitment of blood monocytes [1]. Studies in rodents have shown that adult tissue macrophages are primarily derived from embryonic precursors that seed the tissues prior to birth, not from blood monocytes These tissue-resident macrophages play a central role in homeostasis and maintain themselves by self-renewal [4,5,6,7,8,9]. Tissue-resident macrophages in the intestine and the skin are considered to be largely derived from blood monocytes, which can be explained by the fact that these sites are constantly exposed to the environment being subject to a low grade of mild inflammation These intestinal MDMs contribute to homeostasis by having a high phagocytic and bactericidal activity, but they do not, in contrast to blood monocytes and other tissue macrophages, release proinflammatory cytokines upon phagocytosis [11,12,13]
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