Department of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106, Warsaw, Poland.
Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
Cell Commun Signal. 2024 Nov 27;22(1):570. doi: 10.1186/s12964-024-01929-8.
Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163. Unexpectedly, macrophages do not degrade the entire Hb, but instead transfer it to neighboring cells. We have shown that the phenomenon of Hb transfer from macrophages to other cells is mainly mediated by extracellular vesicles. In contrast to the canonical Hb degradation pathway by macrophages, Hb transfer has not been reported before. In addition, we have used the process of Hb transfer in anticancer therapy, where macrophages are loaded with a Hb-anticancer drug conjugate and act as cellular drug carriers. Both mouse and human macrophages loaded with Hb-monomethyl auristatin E (MMAE) effectively killed cancer cells when co-cultured in vitro.
血红蛋白（Hb）在红细胞内发挥其生理功能。细胞外 Hb 具有促氧化和促炎作用，因此被触珠蛋白隔离，并被巨噬细胞上的 CD163 受体结合。在本研究中，我们证明了巨噬细胞摄取 Hb 的一种新过程，该过程不依赖触珠蛋白和 CD163。出乎意料的是，巨噬细胞不会降解整个 Hb，而是将其转移到邻近的细胞。我们已经表明，Hb 从巨噬细胞转移到其他细胞的现象主要是通过细胞外囊泡介导的。与巨噬细胞经典的 Hb 降解途径不同，Hb 转移以前尚未报道过。此外，我们在抗癌治疗中利用了 Hb 转移的过程，其中巨噬细胞被加载 Hb-抗癌药物偶联物，并充当细胞药物载体。当在体外共培养时，加载 Hb-单甲基澳瑞他汀 E（MMAE）的小鼠和人巨噬细胞有效地杀死了癌细胞。
