The inflammatory role of heparan sulfate proteoglycans in human macrophages

Introduction Heparan sulfate proteoglycans (HSPGs) are near ubiquitously expressed in the extracellular matrix, in basement membranes, and on the surface of cells. This group of molecules has a well‐established role in inflammation due to their ability to bind numerous inflammatory mediators and promote or inhibit their interactions with receptors. For example, on the vascular endothelium, they facilitate the formation of a chemokine gradient to attract circulating leucocytes, while the HSPGs on macrophages have been shown to allow presentation of FGF2 to other cells. However, the role of HSPGs expressed in macrophages is not known, and their expression patterns upon macrophage polarisation and stimulation have similarly not been characterised. Here, we have profiled mRNA expression of HSPG‐associated genes in primary human macrophages. Materials and Methods Monocytes were isolated from human blood and cultured with GM‐CSF or M‐CSF to obtain pro‐inflammatory and anti‐inflammatory macrophage populations, which were then stimulated with LPS. At time intervals, cell lysates were obtained for RNA extraction and generation of cDNA, which was analysed by qPCR using a microarray fluidic card. Results Many of the HS core proteins and biosynthetic enzymes were differentially regulated according to GM‐CSF or M‐CSF polarisation. Moreover, many of these genes showed significant LPS responsiveness in one or both cell types, with some genes being upregulated following LPS treatment and others downregulated. Discussion Our results indicate that HSPGs may have an important role in macrophage phenotype, as the baseline expression of HS‐associated genes differs according to polarisation state. Moreover, the significant changes we observe in the expression levels of HS core proteins and biosynthetic enzymes in response to an inflammatory stimulus suggest that HSPGs undergo remodelling during an inflammatory response and may thus have a role in macrophage functions.