Role of Heparanase in Macrophage Activation

Macrophages represent one of the most diverse immunocyte populations, constantly shifting between various phenotypes/functional states. In addition to execution of vital functions in normal physiological conditions, macrophages represent a key contributing factor in the pathogenesis of some of the most challenging diseases, such as chronic inflammatory disorders, diabetes and its complications, and cancer. Macrophage polarization studies focus primarily on cytokine-mediated mechanisms. However, to explore the full spectrum of macrophage action, additional, non-cytokine pathways responsible for altering macrophage phenotype have to be taken into consideration as well. Heparanase, the only known mammalian endoglycosidase that cleaves heparan sulfate glycosaminoglycans, has been shown to contribute to the altered macrophage phenotypes in vitro and in numerous animal models of inflammatory conditions, occurring either in the presence of microbial products or in the setting of non-infectious "aseptic" inflammation. Here we discuss the involvement of heparanase in shaping macrophage responses and provide information that may help to establish the rationale for heparanase-targeting interventions aimed at preventing abnormal macrophage activation in various disorders.