Shedding Mechanisms Releasing Macrophage Related Biomarkers

Biomarkers reflecting macrophage activity have proving useful tools in diagnostics; and monitoring of disease activity. Numerous reports
have showing that soluble CD163 (sCD163) and more recently; soluble CD206 (sCD206), correlating with disease activity; Especially, sCD163 has been most extensively studying especially in patients suffering from acute and chronic inflammation; such as acute liver failure, hemophagocytic syndrome, HIV, and cancer.

But sCD206 on the other hand is less investigating; but seeming to be increasing especially in patients with acute illness; such as sepsis, organ failure; or severe liver disease9 as well as some cancers; Although sCD163 and sCD206 are often positively correlating and simultaneously increasing in several diseases; patients suffering from severe infections often have elevating levels of sCD206; while retaining normal sCD163 values. In contrast, normal sCD206 and high sCD163 have been reporting in hematological patients; during treatment of axial spondyloarthritis, a decline in sCD163 was observed, whereas sCD206 increasing.

Macrophage related biomarkers

But both the CD163 and CD206 are primarily expressing by macrophages. Although CD163, also known as the hemoglobin haptoglobin scavenger receptor; is involving in the removal of toxic hemoglobin from the circulation; the specific function of CD206 is not
completely understanding. the presence of sCD163 and sCD206 in normal plasma, the soluble receptors have been shown to be present
in cell culture media.

But while sCD206 has been showing to be present in media from both culturing human dendritic cells36 as well as both human and murine macrophages. In addition, studies have showing that LPS39 and PMA35; can induce CD163 shedding in cell cultures; whereas CD206 shedding can be inducing by fungi stimulation. CD163 is shedding by activation of ADAM17/TACE that results in a simultaneous release of sCD163 and TNF-? from the macrophage membrane.

Incubating culturing human

To test the ability of zymosan to induce release of human sCD163 and sCD206, study incubating culturing human; MDMs with zymosan and analyzing the effect on CD163 and CD206 shedding; LPS and zymosan are known inducers of protein kinase C (PKC). Therefore, study evaluating the effects of PMA; another known PKC activator. In vitro PMA stimulation of cultured MDMs resulted in efficient CD163 shedding.

The macrophage deriving soluble receptors sCD163 and sCD206 have proving to be interesting biomarkers in several diseases; including inflammation, cancer, and infections. Even though CD163 and CD206 are both expressing on macrophages and despite reports that levels
of sCD163 and sCD206 often positively correlate; some interesting differences in shedding profiles between the 2 markers have been
observing in clinical samples.