Macrophage Activation Markers, Soluble CD163 and Mannose Receptor, in Liver Fibrosis

Abstract

Macrophages are essential components of the human host immune system, which upon activation facilitates a broad pallet of immunomodulatory events including release of pro- or anti-inflammatory cytokines and chemokines, restoration of immune homeostasis and/or wound healing. Moreover, some macrophage phenotypes are crucially involved in fibrogenesis through stimulation of myofibroblasts, while others promote fibrolysis. During the last decades, the role of resident liver macrophages viz. Kupffer cells and recruited monocytes/macrophages in acute and chronic liver diseases has gained interest and been extensively investigated. Specifically, the scavenger receptors CD163 and mannose receptor (CD206), expressed by macrophages, are of utmost interest since activation by various stimuli induce their shedding to the circulation. Thus, quantifying concentrations of these soluble biomarkers may be of promising clinical relevance in estimating the severity of inflammation and fibrosis and to predict outcomes such as survival. Here, we review the existing literature on soluble CD163 and soluble mannose receptor in liver diseases with a particular focus on their relationship to hepatic fibrosis in metabolic associated fatty liver disease, as well as in chronic hepatitis B and C.

Non-alcoholic fatty liver disease in patients with type 2 diabetes in Greenland: a register-based cross-sectional study

“…In order to affirm the hypothesis that Greenlanders are less likely to develop liver fibrosis than Danes, future studies will benefit from a longitudinal design and require patient cohorts with a larger control group, a larger proportion suffering from moderate and advanced liver fibrosis, and inclusion of Fibroscan® or biopsy specimens for comparison. Also, other promising non-invasive biomarkers of liver steatosis and fibrosis may be relevant to evaluate in Arctic populations in future studies [ 34 ].…”

Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

“…The M-type phospholipase A 2 receptor has a high degree of homology (~30%) to mannose receptors, a member of the lectin receptor family, constitutively expressed in macrophages [38,39]. Mannose receptors are involved in phagocytosis, antigen processing [29,38,40], and the production of inflammatory cytokines by macrophages [40][41][42]. Additionally, this receptor has been demonstrated to play a role in cell proliferation and AA release, via MAPKs (protein kinase activated by the mitogens family), induced by the group IB sPLA 2 s [43][44][45].…”

Soluble CD163 is produced by monocyte-derived and alveolar macrophages, and is not associated with the severity of idiopathic pulmonary fibrosis

“…Although its physiological role remains unknown, sCD163 is recognized as a strong marker for macrophage activation. 1–3 Several clinical studies have indeed reported that blood sCD163 levels are increased in patients with acute inflammatory diseases such as sepsis and acute hepatitis. 1,4 In addition, high serum sCD163 levels could be associated with the severity of chronic fibrotic diseases.…”

“…1,4 In addition, high serum sCD163 levels could be associated with the severity of chronic fibrotic diseases. Increased serum CD163 concentrations constitute a relevant biological marker for aggravation of HBV and HCV-related liver fibrosis 3,5 and interstitial lung disease (ILD) associated with inflammatory myositis. 6 Idiopathic pulmonary fibrosis (IPF) is an irreversible and rapidly fatal diffuse ILD.…”