Abstract
BackgroundCirculating bone marrow-derived monocytes can leave the blood, enter a tissue, and differentiate into M1 inflammatory, M2a remodeling/fibrotic, or M2c/Mreg resolving/immune-regulatory macrophages. Macrophages can also convert from one of the above types to another. Pentraxins are secreted proteins that bind to, and promote efficient clearance of, microbial pathogens and cellular debris during infection, inflammation, and tissue damage. The pentraxins C-reactive protein (CRP), serum amyloid P (SAP), and pentraxin-3 (PTX3) can also bind a variety of endogenous ligands. As monocytes and macrophages are exposed to differing concentrations of pentraxins and their ligands during infection, inflammation, and tissue damage, we assessed what effect pentraxins and their ligands have on these cells.ResultsWe found that many polarization markers do not discriminate between the effects of pentraxins and their ligands on macrophages. However, pentraxins, their ligands, and cytokines differentially regulate the expression of the hemoglobin-haptoglobin complex receptor CD163, the sialic acid-binding lectin CD169, and the macrophage mannose receptor CD206. CRP, a pentraxin generally thought of as being pro-inflammatory, increases the extracellular accumulation of the anti-inflammatory cytokine IL-10, and this effect is attenuated by GM-CSF, mannose-binding lectin, and factor H.ConclusionsThese results suggest that the presence of pentraxins and their ligands regulate macrophage differentiation in the blood and tissues, and that CRP may be a potent inducer of the anti-inflammatory cytokine IL-10.
Highlights
Circulating bone marrow-derived monocytes can leave the blood, enter a tissue, and differentiate into M1 inflammatory, M2a remodeling/fibrotic, or M2 remodeling/fibrotic (M2a) or resolving/immune-regulatory (M2c)/Mreg resolving/immune-regulatory macrophages
These results suggest that pentraxins do not appear to affect the percent of macrophages expressing CD119, MHC class II, CCR7, Interferon regulatory factor 5 (IRF5), Dectin-1, resistin-like molecule-β (RELMβ), Interferon regulatory factor 4 (IRF4), fibronectin, sphingosine kinase-1 (SPK), CD270, or CD172a
We occasionally observed dendritic cells in cultures with Granulocyte Macrophage colony stimulating factor (GM-CSF) (Fig. 3g insert). These results suggest that in cultures with M-CSF or GM-CSF, pentraxins affect the percentage of macrophages expressing detectable levels of CD163, CD169, and CD206
Summary
Circulating bone marrow-derived monocytes can leave the blood, enter a tissue, and differentiate into M1 inflammatory, M2a remodeling/fibrotic, or M2c/Mreg resolving/immune-regulatory macrophages. As monocytes and macrophages are exposed to differing concentrations of pentraxins and their ligands during infection, inflammation, and tissue damage, we assessed what effect pentraxins and their ligands have on these cells. Tissue resident macrophages derive from progenitor cells that develop in the fetal yolk sac and fetal liver, whereas circulating monocytes are bone marrow-derived cells that leave the blood, enter tissues, and differentiate into macrophages during inflammation, infection, or tissue damage [2]. There are different types of macrophages such as M1 inflammatory macrophages, and M2 remodeling/fibrotic (M2a) or resolving/immune-regulatory (M2c; sometimes called Mreg) macrophages [3]. In fibrosis, the macrophages have an M2a pro-fibrotic phenotype, and shifting these to an M2c phenotype could be therapeutic [1, 6]
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