Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells

The human type II collagen (Col II), specifcally expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artifcial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purifed and were treated with high doses of macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), or granulocyte-colony stimulating factor (G-CSF) and examined the Col II expression at indicated days. Quantitative Col II expression was validated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and fow cytometry. We demonstrate that monocytes in PBMNCs can be artifcially induced to express both Col II proteins and M2 macrophage markers by the high concentration of colony-stimulating factors, especially M-CSF and GM-CSF. The Col II proteins were detected on the cell membrane and in the cytoplasm by fow cytometry and immunocytostaining. Combination with IL-4 provided a synergistic efect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double-expressing cells, named modifed macrophages, share M2 macrophages’ anti-infammatory potency. We demonstrated that the modifed macrophages could signifcantly attenuate the infammatory progress of Complete Freund’s adjuvant (CFA)-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the frst evidence that a modifed macrophage population could ectopically express Col II and control the progress of arthritis in animals.