CD163

Fig1. Schematic representation of the three CD163 transmembrane isoforms. (Andriana Plevriti, 2024)

What is CD163 Protein?

CD163 gene (CD163 molecule) is a protein coding gene which situated on the short arm of chromosome 12 at locus 12p13. This gene cranks out a protein that's part of the scavenger receptor family, mainly found in monocytes and macrophages. Its big job? Helping clean up by grabbing and digesting hemoglobin/haptoglobin stuff to shield tissues from oxidative damage caused by free hemoglobin. Besides that, it might also act as an immune lookout, sensing bacteria and kick-starting local inflammation. The CD163 protein is consisted of 1156 amino acids and CD163 molecular weight is approximately 125.5 kDa.

What is the Function of CD163 Protein?

CD163 not only helps remove metabolic waste, it also acts as a sensor for the immune system. It recognizes and responds to the signals of certain bacterial infections, initiates local inflammatory responses, and protects the body from oxidative damage caused by free hemoglobin. We also see it present more in body fluids in some inflammatory diseases, such as cirrhosis, diabetes and sepsis, where its levels are elevated. In addition, CD163 is also expressed in the central nervous system, especially after bleeding, and its role in neurons is still being studied. It can be said that the CD163 protein is not only responsible for cleaning up and recycling bad molecules inside the body, but also participates in our immune defense and inflammatory response to a certain extent.

CD163 Related Signaling Pathway

In general, CD163 recognizes bacteria in the immune system and helps rid the body of pathogens. CD163 plays an important role in the inflammatory response, especially when dealing with hemoglobin that is formed after bleeding. This receptor protects tissue from oxidative damage that can result from free hemoglobin. In addition, the soluble form of CD163 is also increased in the blood in some diseases such as cirrhosis, diabetes, and certain infectious states. Understanding this protein and its role can lead to more in-depth research and treatment of related diseases.

CD163 Related Diseases

CD163 recognizes and binds to hemoglobin-haptoglobin complexes to help clear these complexes and prevent oxidative damage caused by hemoglobin. In addition, it acts as a sensor of innate immunity, detects bacteria and is active in the inflammatory response. Most interestingly, CD163 is increased in inflammatory diseases such as liver cirrhosis, type 2 diabetes, sepsis, and HIV infection. When these conditions occur in the body, we can detect a form called "soluble CD163" in the blood, which is produced by the shear of membrane binding CD163. Studies have found that this soluble form is associated with changes in the condition of a variety of diseases and can even be used to monitor response to treatment.

Bioapplications of CD163

This protein, found primarily in monocytes and macrophages, is responsible for cleaning out the hemoglobin-haptoglobin complex in the blood, which is important for protecting body tissues from oxidative damage caused by free hemoglobin. In addition, it acts as a congenital immune sensor that can sense bacteria and trigger local inflammatory responses. For some inflammation-related diseases, such as cirrhosis, rheumatoid arthritis, and sepsis, levels of lytic CD163 (sCD163) are significantly elevated, making it a potential disease biomarker. In pathological studies, CD163 is also used as a tool to label macrophages, helping researchers understand how these immune cells behave and function in a variety of health and disease states.

Case Study 1: Sara A. Ferreira, 2023

In Parkinson's disease (PD), a couple of key events are the buildup of alpha-synuclein (α-syn) and the activation of the immune system. This immune response involves both brain and peripheral immune cells, but we don't know a lot about which immune proteins play major roles. Researchers think that the increase in CD163 levels seen in blood monocytes and active microglia of PD patients might act as a defense mechanism. To dig deeper into this, researchers used a PD model with mice that had CD163 knocked out (KO) and compared them to their normal littermates. In female CD163KO mice, there was a noticeable early difference in the immune response to α-syn, observed through various analyses. After six months, these CD163KO females had a ramped-up immune reaction and worsening α-syn pathology, leading to more severe dopamine neuron damage.

Fig1. Show error differences between males and females in WT animals.

Fig2. Bar graph showing the number of up/downregulated genes in CD163KO vs. WT females.

Case Study 2: Grant C. O'Connell, 2017

This study looked at how CD163 is involved in suppressing the immune system after a stroke. Researchers checked blood samples from 39 stroke patients, 20 people without neurological issues, and 20 with stroke-like symptoms within 24 hours of when symptoms appeared. They found that people who'd had a stroke had higher levels of ADAM17 activity and soluble CD163 in their blood, which was linked to lower lymphocyte counts after the stroke. Further lab tests suggested that the rise in soluble CD163 might come from activated monocytes because stroke patients' serum caused healthy donor monocytes to release CD163 with the help of ADAM17. More tests showed that this increased soluble CD163 could actually suppress the immune system, as stroke patients' serum halted the growth of lymphocytes from healthy donors, but this effect lessened when CD163 was removed from the serum.

Fig3. Correlation matrix depicting the group-wide collective relationships between peripheral blood ADAM17 mRNA expression, CD163 mRNA expression, ADAM17 activity, and sCD163 levels.

Fig4. Neutrophil-derived sCD163 levels in cell culture supernatants collected following treatment.

CD163 has several biochemical functions, for example, protein binding,scavenger receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CD163 itself. We selected most functions CD163 had, and list some proteins which have the same functions with CD163. You can find most of the proteins on our site.

CD163 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CD163 here. Most of them are supplied by our site. Hope this information will be useful for your research of CD163.

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