Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nat Immunol. 2012 Nov;13(11):1072-82. doi: 10.1038/ni.2408. Epub 2012 Sep 16.
Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells resisted radiation-induced cell death and further upregulated COX-2 expression under stress conditions. COX-2-derived prostaglandin E(2) (PGE(2)) prevented HSPC exhaustion by limiting the production of reactive oxygen species (ROS) via inhibition of the kinase Akt and higher stromal-cell expression of the chemokine CXCL12, which is essential for stem-cell quiescence. Our study identifies a previously unknown subset of α-SMA(+) activated monocytes and macrophages that maintain HSPCs and protect them from exhaustion during alarm situations.
造血干细胞和祖细胞（HSPCs）受各种骨髓基质细胞类型的调节。在这里，我们鉴定出了稀有活化的骨髓单核细胞和巨噬细胞，它们高表达α-平滑肌肌动蛋白（α-SMA）和环氧化酶 COX-2，与原始 HSPCs 相邻。这些髓样细胞抵抗辐射诱导的细胞死亡，并在应激条件下进一步上调 COX-2 的表达。COX-2 衍生的前列腺素 E2（PGE2）通过抑制激酶 Akt 和更高的趋化因子 CXCL12 的基质细胞表达，限制活性氧（ROS）的产生，从而防止 HSPC 耗竭，CXCL12 对于干细胞静止是必需的。我们的研究鉴定出了一个以前未知的 α-SMA（+）活化单核细胞和巨噬细胞亚群，它们维持 HSPCs 并在警报情况下防止它们耗竭。
