School of Dentistry, University of Michigan, Ann Arbor, MI 48109; Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI 48109; and
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115.
J Immunol. 2014 Jul 1;193(1):26-9. doi: 10.4049/jimmunol.1301945. Epub 2014 Jun 2.
Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly defined mechanisms. Specialized proresolving mediators of inflammation drive macrophage efferocytosis (phagocytosis of apoptotic cells) and resolution, but little is known regarding this process in the bone marrow. In this study, metabololipidomic profiling via liquid chromatography mass spectrometry revealed higher levels of specialized proresolving mediators in the bone marrow relative to the spleen. The endocrine and bone anabolic agent parathyroid hormone increased specialized proresolving mediator levels, including resolvins (Rvs), in bone marrow. Human and murine primary macrophages efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM-10 nM) enhanced this process. These findings support a unique profile of specialized lipid mediators in bone marrow that contribute to a feedback system for resolution of inflammation and maintenance of skeletal homeostasis.
骨髓巨噬细胞通过尚未明确的机制刺激骨骼伤口修复和成骨细胞形成。炎症的专门促解决介质可驱动巨噬细胞吞噬作用(凋亡细胞的吞噬作用)和解决,但对于骨髓中的这个过程知之甚少。在这项研究中,通过液相色谱-质谱法进行的代谢脂质组学分析显示,骨髓中专门的促解决介质水平高于脾脏。内分泌和骨骼合成代谢剂甲状旁腺激素增加了骨髓中的专门促解决介质水平,包括 resolvins(Rvs)。人和鼠原代巨噬细胞在体外吞噬凋亡的成骨细胞,RvD1 和 RvD2(10 pM-10 nM)增强了这一过程。这些发现支持了骨髓中专门脂质介质的独特特征,有助于炎症解决和骨骼内稳态维持的反馈系统。