Hemolysis and immune regulationZhong, Hui; Yazdanbakhsh, KarinaCurrent Opinion in Hematology: May 2018 - Volume 25 - Issue 3 - p 177–182 doi: 10.1097/MOH.0000000000000423 ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Abstract Author InformationAuthors Article MetricsMetrics Purpose of review Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders. Recent findings Plasma-free heme can induce the formation of neutrophil extracellular traps (NETs) through reactive oxygen species signaling. Although NETs protect the host against infections, in patients with sickle disease, they are associated with vaso-occlusive crises. Heme may increase host susceptibility to infections by inducing heme oxygenase 1 (HO-1) in immature neutrophils, thereby inhibiting oxidative burst required for clearance of engulfed bacteria. In addition, heme impairs macrophage phagocytosis and microbial clearance through inhibition of cytoskeletal remodeling. Hemolysis can also favor anti-inflammatory immune cell polarization by inhibiting dendritic cell maturation necessary for effector T-cell responses, inducing differentiation of monocytes into red pulp macrophages, important for iron recycling from senescent erythrocytes, and driving regulatory T-cell expansion through modulation of HO-1 expression in nonclassical monocytes. Summary Hemolysis breakdown products show remarkable effects on the regulation of immune cell differentiation and function. Laboratory of Complement Biology, New York Blood Center, New York, New York, USA Correspondence to Hui Zhong, Laboratory of Complement Biology, New York Blood Center, 310 E 67th Street, New York, NY 10065, USA. Tel: +1 212 570 3383; fax: +1 212 737 4506; e-mail: email@example.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.