Regulation of CD163 expression in human macrophages in diabetic conditions

Abstract

Scavenging function of monocytes and macrophages is essential for the control of inflammatory reactions. The monocyte- and macrophage-specific scavenger receptor CD163 internalizes and degrades haemoglobin-haptoglobin complexes built due to intravascular haemolysis. This circumstance particularly occurs in inflammation, supporting the development of microvascular diabetic complications. The shedding of CD163 from the cell surface in inflammation leads to an impaired scavenging function and consequently increases the risk of vascular oxidative damage. The project aims to examine how high glucose conditions affect the CD163-mediated scavenging of human primary differentially activated macrophages. CD14+-monocytes were isolated from the peripheral blood of healthy donors by density gradient centrifugation and magnetic separation. M0 (non-stimulated), M1 (IFNgamma-stimulated) and M2 (IL-4-stimulated) macrophages were differentiated within 6 days in low (5mM) and high (25mM) glucose conditions. CD163-mRNA expression was quantified by qRT-PCR. CD163 surface expression was analysed by flow cytometry. Increased glucose had a suppressing effect on CD163 mRNA expression in 8 out of 10 donors in M1; and in 7 out of 10 donors in M2. The suppressive effect of glucose was more pronounced in M2 compared to M1. Regarding surface expression, the effect of high glucose was donor-dependent in M0 and M2, whereas the expression of CD163 uniformly decreased in M1. Our data suggest that elevated glucose levels affect both transcriptional and posttranscriptional mechanisms of CD163 production in a donor-specific manner. We concluded that the suppression of CD163 expression in macrophages by high glucose can contribute to the development of inflammation-mediated complications in diabetic patients.