AM-3K, an Anti-macrophage Antibody, Recognizes CD163, a Molecule Associated with an Anti-inflammatory Macrophage Phenotype

Abstract

CD163 is a member of the scavenger receptor cysteine-rich superfamily restricted to the monocyte/macrophage lineage and is thought to be a useful marker for anti-inflammatory or alternatively activated macrophages. In this study we used mass spectrometric analysis to determine that the antigen recognized by the antibody AM-3K, which we previously generated as a tissue macrophage-specific monoclonal antibody, was CD163. An anti-inflammatory subtype of macrophages stimulated by dexamethasone or interleukin-10 showed strong reactivity for AM-3K and increased expression of CD163 mRNA. Immunohistochemical staining of routinely processed pathological specimens revealed that AM-3K recognized a specialized subpopulation of macrophages. In granulomatous diseases such as tuberculosis, sarcoidosis, or foreign body reactions, tissue macrophages around granulomas, but not component cells of the granulomas such as epithelioid cells and multinucleated giant cells, showed positive staining for AM-3K. In atherosclerotic lesions, scattered macrophages in diffuse intimal lesions were strongly positive for AM-3K, whereas foamy macrophages in atheromatous plaques demonstrated only weak staining. We therefore suggest that, in routine pathological specimens, AM-3K is a useful marker for anti-inflammatory macrophages because these cells can be distinguished from inflammatory or classically activated macrophages. Because AM-3K cross-reacts with macrophage subpopulations in different animal species including rats, guinea pigs, rabbits, cats, dogs, goats, pigs, bovine species, horses, monkeys, and cetaceans, it will have wide application for detection of CD163 in various animals.

Human peritoneal macrophages show functional characteristics of M‐CSF‐driven anti‐inflammatory type 2 macrophages

“…1A). CD163 has been shown to be associated with an anti-inflammatory MU phenotype, either alternatively activated MU or those tissue MU isolated from patients with granulomatous disease [13]. Our finding that MU2 express CD163 confirms the association of CD163 with antiinflammatory activities.…”

HIV-1 Proteins Preferentially Activate Anti-Inflammatory M2-Type Macrophages

“…Despite the unresolved issue, our novel finding that Nef reduced the expression of CD163 and phagocytic activity of M2-MF (Fig. 6), both of which are characteristics of M2-MF (13,36,51,52), strongly suggests that Nef drives anti-inflammatory M2-MF toward MF with an M1-like phenotype.…”

“…6A), the high expression of which is one of the characteristics of M2-MF (51,52). Although the surface expression levels of another scavenger receptor CD204, as well as HLA-DR, were also reduced, the degree was moderate compared with that of CD163 (Fig.…”

Clinicopathological correlation of tumor-associated macrophages in Ewing sarcoma

“…24 ). CD68 is considered to be a pan-macrophage marker and CD163 was reported to show promising signs of being a somewhat specific marker of M2 macrophages 31,32 . However, our study suggests these assumptions may not be generally applicable.…”

“…Furthermore, CD163-positive macrophages may in some cases outnumber CD68-positive cells 37,41 as indicated by our study. Many reports have used CD163 for identification of M2 macrophages 14,16,17,31,32 . However some studies have suggested, as well as our results, that CD163, being a good marker for TAMs in general, cannot be considered an exclusive marker of M2 macrophages when used on its own 37,38 .…”