Promising therapy for fatal sickle cell disease complication
An NIEHS-funded study in mice showed how chlorine exposure leads to Acute Chest Syndrome (ACS), a leading cause of death in patients with sickle cell disease (SCD). The results point to a potential lifesaving therapy for SCD patients exposed to chlorine. Chlorine is found in some household cleaning products and is commonly encountered in industrial accidents and chemical warfare.
SCD is a group of blood disorders in which the hemoglobin protein is defective, causing red blood cells (RBCs) to rupture. The researchers used genetically engineered mice that resembled SCD in humans (sickle mice) and compared them to healthy control mice with human hemoglobin. They exposed both groups to chlorine gas or normal air and assessed survival, lung injury, and hemolysis, or the rupture of RBCs which releases hemoglobin into the blood. They repeated this process but injected mice with hemopexin, which binds to hemoglobin.
Within six hours of chlorine exposure, 64 percent of sickle mice died while none of the controls died. Compared to controls, surviving sickle mice had hemolysis and lung injury. Hemolysis resulted in increased blood levels of heme, a component of hemoglobin known to cause lung injury. Hemopexin treatment following exposure significantly improved survival and reduced blood heme levels and lung injury. RBCs from chlorine-exposed sickle mice had high carbonylation, which increases cell rupture. Carbonylation was absent after hemopexin treatment.
According to the authors, results indicate that chlorine exposure induces ACS-like outcomes in sickle mice and that hemopexin treatment after exposure reduces death and lung injury.
Citation: Alishlash AS, Sapkota M, Ahmad I, Maclin K, Ahmed NA, Molyvdas A, Doran S, Albert CJ, Aggarwal S, Ford DA, Ambalavanan N, Jilling T, Matalon S. 2021. Chlorine inhalation induces acute chest syndrome in humanized sickle cell mouse model and ameliorated by postexposure hemopexin. Redox Biol 44:102009.