Gene expression of cytokines and wound-healing potential of macrophages derived from rat bone marrow and peripheral blood

BACKGROUND: Macrophages are key regulators of inflammation and tissue regeneration and represent a promising tool for cell therapy. In rats, functional differences between macrophages derived from red bone marrow and peripheral blood remain insufficiently studied, particularly in the context of wound healing, where L-arginine metabolism plays a critical role. AIM: To compare the expression levels of regulatory and proinflammatory cytokine genes (interleukin-1β, -6, and -10) and genes encoding L-arginine–metabolizing enzymes (Arg1 and NOS2) in macrophages derived from bone marrow monocyte precursors and peripheral blood monocytes, and to assess their effects on cutaneous wound healing. METHODS: Macrophages were generated from red bone marrow monocyte precursors and peripheral blood monocytes of Sprague–Dawley rats using recombinant macrophage colony-stimulating factor (rM-CSF). Macrophage phenotype was established using immunocytochemistry (staining for CD68 and CD43 markers). Gene expression levels were determined by real-time polymerase chain reaction and normalized to β2-microglobulin (β2M). The effects of macrophages on cutaneous wound healing were evaluated in vivo. Statistical analysis was performed using the Mann–Whitney U test (p 0.05). RESULTS: Macrophages from both sources expressed CD68 and CD43. Red bone marrow (RBM)–derived macrophages demonstrated higher expression levels of IL-6 and IL-10 genes (p = 0.029 and p = 0.027, respectively), whereas peripheral blood (PB)–derived MPs showed higher expression of Arg1 and NOS2 (p = 0.029 for both genes). Administration of PB-derived macrophages did not result in complications, whereas RBM-derived macrophages were associated with wound bleeding. No accelerated wound healing was observed in either group. CONCLUSION: RBM-derived macrophages exhibit enhanced activation potential, whereas PB-derived macrophages demonstrate a more pronounced influence on tissue regeneration. For cell-based therapy, PB-derived macrophages appear preferable due to a lower risk of complications. These findings highlight the importance of further investigation into the source-dependent activity of macrophages in reparative processes.