Guanylate‐binding protein 5 is a marker of interferon‐γ‐induced classically activated macrophages

Abstract

Macrophage activation is the main immunological process occurring during the development of several diseases, and the heterogeneity of macrophage activation or differentiation has been suggested to be involved in disease progression. In the present study, we attempted to identify molecules specifically expressed on human classically activated macrophages (M1) to investigate the significance of the M1-like phenotype in human diseases. Human monocyte-derived macrophages were differentiated into M1, M2a, M2b and M2c phenotypes, and also M1(−) (the M1 phenotype differentiated with interferon-γ) to eliminate the strong effects of lipopolysaccharides (LPS) on the gene expression profile. The gene expression profiles of those macrophage phenotypes were analyzed by a cDNA microarray analysis and were used for a bioinformatics examination to identify the markers of the M1 phenotype that are expressed in both M1 and M1(−). The gene expression profiles of murine macrophages were also evaluated. We identified guanylate-binding protein 5 (GBP5), which is associated nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3)-mediated inflammasome assembly in the M1 macrophages of both humans and mice. Notably, the expression of GBP5 protein was detected in cultured M1(−) as well as in M1 macrophages by western blotting, which means that GBP5 is a more generalized marker of the M1 phenotype compared with the M1 markers that can be induced by LPS stimulation. GBP5 is a useful candidate marker of the M1 phenotype.

Mesenchymal Stromal Cells Are More ImmunosuppressiveIn VitroIf They Are Derived from Endometriotic Lesions than from Eutopic Endometrium

“…CD14 is involved in the uptake of apoptotic cells, CD163 is involved in the uptake of haptoglobin-hemoglobin complexes, and both have crucial roles in clearing up the pelvic cavity from apoptotic cells and heme-iron that accumulates by dying red blood cells, respectively [ 45 , 48 ]. Elevated CD163 expression has been suggested to be a marker of M2c, a subtype of M2 macrophages involved in immunosuppression, matrix deposition, and tissue remodeling [ 20 , 49 – 51 ]. Therefore, increased M2c levels may explain the extensive fibrosis that occurs in endometriotic lesions [ 52 ].…”

M2b macrophage polarization and its roles in diseases

“…LPS plus IC is the classical inducer of M2b macrophage polarization . IL‐1β in combination with IC is also used to induce macrophage polarization to M2b in vitro . Additionally, DSS, a polyanionic derivative of dextran, which is usually employed as an inducer in the colitis model, can induce increases in LIGTH and IL‐10 (biomarkers of M2b) in mice peritoneal macrophages in vitro .…”

“…[6][7][8]11,43,71,75,90 IL-1 in combination with IC is also used to induce macrophage polarization to M2b in vitro. 8,11,41,140,164 Additionally, DSS, a polyanionic derivative of dextran, which is usually employed as an inducer in the colitis model, can induce increases in LIGTH and IL-10 (biomarkers of M2b) in mice peritoneal macrophages in vitro. 48 In addition, ALD-DNA, HK-SA, orosomucoid 1 (ORM1), and serum amyloid-A (SAA) can switch mouse and human macrophages from other phenotypes to the M2b subtype in vitro.…”

Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade

“…Guanylate-binding protein (GBP)-5 is a marker of IFNγ-induced, classically activated human macrophages (28). Although our study is focused on a murine model, we saw significantly higher levels of GBP transcripts in responding tumors, including those of GBP2 (4-fold), GBP2b (50.6-fold), GBP3, GBP4, GBP5, GBP6, GBP7, GBP8, and GBP9 on CD45 + cells, with GBP2b present exclusively in responders (Fig.…”