Corticosteroid receptors, macrophages and cardiovascular disease

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   Figure 1

   Development and differentiation of macrophages. Bone marrow-derived monocytes enter peripheral blood and circulate for several days in an inert state before entering tissues and differentiating into tissue resident macrophages. Tissue resident macrophages include histiocytes (connective tissue), microglial cells (nervous system), Kupffer cells (liver) and osteoclasts (bone). Macrophages are recruited to tissues to restore resident populations or respond to diverse inflammatory and immune stimuli. The acquired phenotype of recruited macrophages reflects signals from the microenvironment in which they reside. These macrophages are broadly classified as classically or alternatively activated macrophages. M-CSF, macrophage colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor.
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   Figure 2

   MR and GR signalling in macrophages and endothelial cells. Macrophages contain functional mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) but not the aldosterone specificity-conferring enzyme, 11βHSD2. Given that glucocorticoids (cortisol in humans and corticosterone in rodents) circulate at much higher concentrations than the mineralocorticoid aldosterone, under normal circumstances the MR in macrophage would be occupied by cortisol. In contrast, endothelial cells contain the enzyme 11βHSD2, hence the MR in endothelial cells is normally activated by aldosterone.
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   Figure 3

   Classical and alternative activation of macrophages. Polarised phenotypes of macrophages are broadly defined as classically and alternatively activated. Classically activated macrophages respond to interferon-γ (INF-γ) and lipopolysaccharide (LPS) and play important roles in type I inflammation, destruction of tissue, killing of intracellular parasites and tumour resistance. In contrast, alternatively activated macrophages response to factors such as IL-4 or IL3, immune complexes, IL-10, TGF-β and glucocorticoids and contribute to type II inflammation, tissue remodelling, angiogenesis, parasite encapsulation and tumour progression.

• © 2009 Society for Endocrinology