Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands; Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
Thromb Res. 2014 Mar;133(3):390-5. doi: 10.1016/j.thromres.2013.10.039. Epub 2013 Nov 1.
Joint bleedings result in iron-mediated synovitis and cartilage destruction. Monocyte/macrophage polarization affects their role in iron homeostasis. This study evaluates the effects of hemarthrosis on monocyte/macrophage polarization.
Using a murine hemophilia model of acute joint bleeding and flow cytometry, we evaluated monocyte/macrophage polarization in blood, spleen, synovium, and knee lavage at day 1, 2, and 7 following the induction of hemarthrosis.
Induction of hemarthrosis resulted in a transient shift of blood monocytes towards a M1 type (control 13 vs. 1847 counted cells at day 1; p<0.01), a temporary decrease of spleen M1 monocytes (control 2841 vs. 1086 counted cells at day 1; p=0.02), and a sustained decrease of spleen M2 red pulp macrophages (control 1853 vs. 673 counted cells at day 7; p=0.01). In addition, an increase in M1 (control 119 vs. 592 counted cells at day 1; p=0.04) and M2 (control 247 vs. 650 counted cells at day 1; p=0.02) synovial macrophages was noted. In the joint lavage, a temporary increase in M1 monocytes (control 20 vs. 125 counted cells at day 1; p=0.04) and a more sustained increase in M2 monocytes (control 73 vs. 186 counted cells at day 2; p<0.01) was observed.
This study demonstrates alterations in monocyte/macrophage polarization following hemarthrosis resulting in a blood monocyte M1 phenotype and a combined M1-M2 monocyte/macrophage phenotype in the joint. Based on the different capabilities of M1 and M2 cells, modulating polarization of distinct monocyte/macrophage populations might represent interesting prophylactic or therapeutic approaches for joint bleedings.
关节出血导致铁介导的滑膜炎和软骨破坏。单核细胞/巨噬细胞极化影响其在铁稳态中的作用。本研究评估了关节积血对单核细胞/巨噬细胞极化的影响。
使用急性关节出血的小鼠血友病模型和流式细胞术，我们在关节积血诱导后第 1、2 和 7 天评估了血液、脾脏、滑膜和膝关节灌洗液中的单核细胞/巨噬细胞极化。
关节积血导致血液单核细胞向 M1 型短暂转移（对照 13 与第 1 天 1847 个计数细胞；p<0.01），脾脏 M1 单核细胞暂时减少（对照 2841 与第 1 天 1086 个计数细胞；p=0.02），脾脏 M2 红髓巨噬细胞持续减少（对照 1853 与第 7 天 673 个计数细胞；p=0.01）。此外，还观察到 M1（对照 119 与第 1 天 592 个计数细胞；p=0.04）和 M2（对照 247 与第 1 天 650 个计数细胞；p=0.02）滑膜巨噬细胞增加。在关节灌洗液中，观察到 M1 单核细胞暂时增加（对照 20 与第 1 天 125 个计数细胞；p=0.04）和 M2 单核细胞持续增加（对照 73 与第 2 天 186 个计数细胞；p<0.01）。
本研究表明关节积血后单核细胞/巨噬细胞极化发生改变，导致血液单核细胞出现 M1 表型，关节中出现 M1-M2 单核细胞/巨噬细胞表型。基于 M1 和 M2 细胞的不同能力，调节不同单核细胞/巨噬细胞群体的极化可能是关节出血的一种有前途的预防或治疗方法。
