Patients with sickle cell disease suffer from ongoing hemolysis because their red cells are fragile, causing them to fall apart and release their contents, which can damage the blood vessels. The sickle red blood cells are also sticky and when they attach to the damaged blood vessels, they can obstruct blood flow, causing the patient to have devastatingly painful episodes, called crises. In a paper published in a recent Blood journal, a group of scientists led by Dr. Yunfeng Liu from Dr. Karina Yazdanbakhsh’s Laboratory of Complement Biology at LFKRI have identified a subset of blood mononuclear cells called patrolling monocytes, which protect against sickle cell pain crisis. Using labeling experiments, the authors demonstrated that these patrolling monocytes directly engulf and remove hemolysis-damaged cells of the blood vessels, and change their molecular profile by expressing high levels of a protective enzyme called heme oxygenase 1, which the authors refer to as HO-1hi. The numbers of these HO-1hi patrolling monocytes were found to be much lower in patients with sickle cell disease experiencing pain crisis, consistent with the notion that inappropriately low HO-1hi patrolling monocytes may predispose patients to painful crisis.
The critical role of HO-1hi patrolling monocytes in protecting against sickle cell pain crisis was further supported in experimental models: lack of patrolling monocyte numbers increased hemolysis-driven blood vessel obstruction caused by sickle red blood cells, whereas increasing the patrolling monocyte numbers partially reversed the obstruction. Ongoing studies by scientists at LFKRI include testing the diagnostic potential of these patrolling monocytes to pre-screen patients with sickle cell disease at risk of pain crisis and more importantly their use as a potential cure for painful crisis for this highly vulnerable patient population.
The study was funded by NIH/NHLBI grants. Co-authors include LFKRI scientists Fangmiao Jing, Dr. Woelsung Yi, Dr. Avital Mendelson and Dr. Patricia Shi as well as our clinical collaborators at the Children's Hospital of Philadelphia, Montefiore Medical Center, and Albert Einstein College of Medicine. The article was highlighted as a Commentary in Blood.
HO-1hi Patrolling Monocytes Protect Against Vaso-Occlusion in Sickle Cell Disease
Yunfeng Liu, Fangmiao Jing, Woelsung Yi, Avital Mendelson, Patricia Shi, Ronald Walsh, David F. Friedman, Caterina Minniti, Deepa Manwani, Stella T. Chou and Karina Yazdanbakhsh. Blood 2018 131:1600-1610.
Hemolysis in sickle cell disease results in the release of free heme (small black circles), which causes blood vessel cell (endothelial cell) damage. Patrolling monocytes bind to the endothelium and engulf damaged cells (red remnants), and in doing so increasing their protective HO-1 levels. If patrolling monocytes are low or missing, the damaged vessel cells attract other cells including granulocytes, causing obstruction of the vessel and precipitation of painful crisis.