CD163 Marker in Macrophages and Inflammation

CD163 is a scavenger receptor expressed on specific macrophages, playing a key role in immune regulation and inflammation resolution. It clears hemoglobin-haptoglobin complexes, preventing oxidative damage and aiding tissue protection. Researchers study CD163 as a biomarker for inflammatory conditions, including infections, autoimmune diseases, and cancer.

Its distinct expression and function make CD163 a crucial indicator of macrophage activity in various physiological and pathological contexts. Understanding its roles and detection methods provides insight into immune system dynamics and disease progression.

Structure And Expression

CD163 is a transmembrane glycoprotein in the scavenger receptor cysteine-rich (SRCR) superfamily, characterized by nine SRCR repeats that bind hemoglobin-haptoglobin complexes. This function allows macrophages to clear free hemoglobin and reduce oxidative stress. The receptor also has a short cytoplasmic tail involved in intracellular signaling and endocytosis. Post-translational modifications, such as glycosylation, affect its stability and function.

CD163 expression is primarily restricted to monocytes and macrophages, with high levels in tissue-resident macrophages like Kupffer cells in the liver, red pulp macrophages in the spleen, and certain placental populations. Anti-inflammatory cytokines, particularly interleukin-10 (IL-10) and glucocorticoids, enhance its surface expression, while pro-inflammatory stimuli like lipopolysaccharides (LPS) and tumor necrosis factor-alpha (TNF-α) induce shedding of its extracellular domain, producing soluble CD163 (sCD163), which circulates in the bloodstream.

Metalloproteinases such as ADAM17 mediate CD163 shedding under inflammatory conditions, modulating receptor availability and immune signaling. The balance between membrane-bound and soluble CD163 influences macrophage function, with elevated sCD163 linked to conditions like sepsis, liver fibrosis, and atherosclerosis.

Association With Macrophage Function

CD163 defines macrophage activity, particularly in tissue repair and homeostasis. Associated with the M2 macrophage phenotype, it facilitates hemoglobin-haptoglobin clearance, preventing oxidative stress and supporting iron recycling. This function is critical in organs with high erythrocyte turnover, such as the liver and spleen.

Beyond hemoglobin scavenging, CD163 promotes anti-inflammatory pathways. Its expression increases in response to IL-10 and glucocorticoids, leading to secretion of anti-inflammatory mediators like transforming growth factor-beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra). CD163 also enhances macrophage survival, making these cells prevalent in chronic wounds, fibrotic tissues, and tumor-associated macrophages, where they contribute to matrix remodeling and angiogenesis.

Certain pathogens exploit CD163 as an entry receptor, allowing them to evade immune clearance. For example, porcine reproductive and respiratory syndrome virus (PRRSV) uses CD163 to infect macrophages. Shedding dynamics further influence macrophage activation, with increased sCD163 levels signaling systemic immune shifts.

Relation To Inflammatory Processes

CD163 plays a critical role in resolving inflammation and modulating immune responses. It helps maintain homeostasis by clearing hemoglobin-haptoglobin complexes and reducing oxidative stress. Anti-inflammatory cytokines like IL-10 and glucocorticoids enhance CD163 expression, fostering tissue repair, while pro-inflammatory signals such as TNF-α and LPS promote its shedding, generating sCD163 as a marker of macrophage activation.

Elevated sCD163 levels are associated with inflammatory diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. In sepsis, high sCD163 levels correlate with macrophage activation and disease severity. In rheumatoid arthritis, persistent sCD163 elevation reflects macrophage-driven tissue remodeling. In cardiovascular disease, increased sCD163 signals plaque instability and macrophage activity in atherosclerotic lesions.

CD163 also contributes to inflammatory resolution by modulating macrophage responses to tissue injury. In liver fibrosis, CD163-expressing macrophages reduce hepatocellular damage by limiting oxidative stress. In neuroinflammatory diseases like multiple sclerosis, CD163-positive macrophages appear in lesion sites, supporting tissue repair while suppressing inflammation.

Laboratory Detection Approaches

CD163 detection relies on several techniques. Immunohistochemistry (IHC) is widely used to visualize CD163 in tissue samples, identifying macrophage distribution and density in pathological conditions. This method employs monoclonal antibodies to bind CD163 on fixed tissue sections, followed by enzyme or fluorescence-based detection.

Flow cytometry provides quantitative analysis of CD163 expression on macrophages in blood or tissue samples. Using fluorescently labeled antibodies, it allows high-throughput measurement of CD163 levels and co-expression with other macrophage markers. This method is useful for distinguishing macrophage subsets and monitoring responses to therapy.

Enzyme-linked immunosorbent assay (ELISA) is the primary tool for measuring soluble CD163 (sCD163) in serum or plasma. ELISA kits use capture antibodies to bind sCD163, generating a quantifiable signal. This method is extensively used in clinical research to track disease progression and treatment response. Standardization is essential to account for variability in sCD163 levels due to sample handling and diurnal fluctuations.

Relevance In Immune Profiling

CD163 is a valuable marker for immune profiling, distinguishing macrophage subsets involved in anti-inflammatory and tissue-repair processes. By assessing CD163 in blood, tissue, or fluid samples, researchers and clinicians can evaluate macrophage activity in diseases such as cancer, autoimmune disorders, and chronic infections.

One key application is monitoring disease progression and treatment response. Elevated sCD163 levels are observed in conditions like sepsis, HIV, and liver fibrosis, reflecting macrophage activation. In oncology, tumor-associated macrophages often show increased CD163 expression, correlating with tumor progression and immune suppression. This has led to studies on its potential as a prognostic biomarker in cancers such as glioblastoma and colorectal carcinoma. In autoimmune diseases like systemic lupus erythematosus and multiple sclerosis, CD163 fluctuations help assess disease activity and therapy effectiveness.

As research advances, CD163 remains a promising target for refining immune profiling strategies in both clinical and research settings.