Singhal Rashi, Chawla Sheetal, Rathore Deepak K, Bhasym Angika, Annarapu Gowtham K, Sharma Vandana, Seth Tulika, Guchhait Prasenjit
Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India; Department of Biotechnology, Manipal University, Karnataka, India.
Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.
Clin Immunol. 2017 Feb;175:133-142. doi: 10.1016/j.clim.2016.12.007. Epub 2016 Dec 28.
Monocytes and macrophage combat infections and maintain homeostatic balance by engulfing microbes and apoptotic cells, and releasing inflammatory cytokines. Studies have described that these cells develop anti-inflammatory properties upon recycling the free-hemoglobin (Hb) in hemolytic conditions. While investigating the phenotype of monocytes in two hemolytic disorders-paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD), we observed a high number of pro-inflammatory (CD14CD16) monocytes in these patients. We further investigated in vitro the phenotype of these monocytes and found an estimated 55% of CD14 cells were transformed into the CD14CD16 subset after engulfing Hb-activated platelets. The CD14CD16 monocytes, which were positive for both intracellular Hb and CD42b (platelet marker), secreted significant amounts of TNF-α and IL-1β, unlike monocytes treated with only free Hb, which secreted more IL-10. We have shown recently the presence of a high number of Hb-bound hyperactive platelets in patients with both diseases, and further investigated if the monocytes engulfed these activated platelets in vivo. As expected, we found 95% of CD14CD16 monocytes with both intracellular Hb and CD42b in both diseases, and they expressed high TNF-α. Furthermore our data showed that these monocytes whether from patients or developed in vitro after treatment with Hb-activated platelets, secreted significant amounts of tissue factor. Besides, these CD14CD16 monocytes displayed significantly decreased phagocytosis of E. coli. Our study therefore suggests that this alteration of monocyte phenotype may play a role in the increased propensity to pro-inflammatory/coagulant complications observed in these hemolytic disorders-PNH and SCD.
单核细胞和巨噬细胞通过吞噬微生物和凋亡细胞以及释放炎性细胞因子来对抗感染并维持体内稳态平衡。研究表明，在溶血条件下循环利用游离血红蛋白（Hb）时，这些细胞会产生抗炎特性。在研究两种溶血性疾病——阵发性夜间血红蛋白尿（PNH）和镰状细胞病（SCD）中单核细胞的表型时，我们观察到这些患者中有大量促炎（CD14CD16）单核细胞。我们进一步在体外研究了这些单核细胞的表型，发现约55%的CD14细胞在吞噬Hb激活的血小板后转化为CD14CD16亚群。与仅用游离Hb处理的单核细胞分泌更多IL-10不同，同时表达细胞内Hb和CD42b（血小板标志物）的CD14CD16单核细胞分泌大量TNF-α和IL-1β。我们最近已表明这两种疾病患者中存在大量与Hb结合的高活性血小板，并进一步研究了单核细胞在体内是否吞噬这些活化血小板。正如预期的那样，我们在这两种疾病中均发现95%的CD14CD16单核细胞同时表达细胞内Hb和CD42b，并且它们高表达TNF-α。此外，我们的数据表明，这些单核细胞无论是来自患者还是在体外经Hb激活的血小板处理后产生的，都分泌大量组织因子。此外，这些CD14CD16单核细胞对大肠杆菌的吞噬作用明显降低。因此，我们的研究表明，单核细胞表型的这种改变可能在这些溶血性疾病——PNH和SCD中观察到的促炎/促凝并发症增加倾向中起作用。
