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

Abstract The human type II collagen (Col II), specifically expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artificial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purified 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 flow cytometry. The subpopulation of the cytokine-induced Col II-expression cells were examined by the maturation markers of macrophages by flow cytometry. Complete Freund’s adjuvant (CFA)- and collagen-induced arthritis in rodents were subjected for the anti-inflammatory assays of Col II-expressing cells. We demonstrate that monocytes in PBMNCs can be artificially induced to express both Col II proteins and M2 macrophage markers by high concentration of colony stimulating factors, especially M-CSF and GM-CSF. Combination with IL-4 provides a synergistic effect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double expressing cells, named as modified macrophages, significantly attenuated the inflammatory progress of CFA-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the first evidence that a population of modified macrophages could ectopically express Col II to control the progress of arthritis in animals.