Triggering factors of Acute Chest Syndrome (ACS) is a leading cause of death in patients with Sickle Cell Disease (SCD) and targeted therapies are limited. Chlorine (Cl2) inhalation happens frequently, but its role as a potential trigger of ACS has not been determined. In this study, we hypothesized that Cl2 exposure resembling that in the vicinity of industrial accidents induces acute hemolysis with acute lung injury, reminiscent of ACS in humanized SCD mice. When exposed to Cl2 (500 ppm for 30 min), 64% of SCD mice succumbed within 6 h while none of the control mice expressing normal human hemoglobin died (p
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Highlights • Chlorine inhalation induces exaggerated hemolysis in sickle mice. • Free heme results in fatal acute chest syndrome in sickle versus control mice. • Chlorinated lipids mediate the effects of chlorine on the red blood cells. • Hemopexin alleviates chlorine induced hypoxia, and acute lung injury. • Therefore, postexposure hemopexin injection improves the survival of sickle mice.