Damaged red blood cells can trigger inflammation

When red blood cells break down through a process called hemolysis, they release a component called heme, which can trigger inflammation and damage tissues and blood vessels. Researchers at Lund University have discovered how heme activates an inflammatory reaction in the blood. This finding could be significant for diseases and conditions involving extensive red blood cell breakdown, such as hemolytic uremic syndrome and malaria.

Heme is a vital part of hemoglobin, the protein responsible for oxygen transport in red blood cells. Once released from the red blood cell, heme becomes harmful and can contribute to inflammation. Hemolysis can occur in various conditions, including sickle cell anemia, malaria, trauma, burns, and mechanical stress on the blood, such as during cardiopulmonary bypass or exposure to mechanical heart valves.

In their study published in Kidney International, the researchers found that heme binds to and activates a protein called factor XII, which in turn activates an inflammatory protein system called the kallikrein-kinin system. This system leads to the release of bradykinin, a molecule that causes blood vessels to dilate and become more permeable, resulting in fluid leaking into surrounding tissues and causing swelling, inflammation, and a drop in blood pressure.

The researchers studied blood samples from children with hemolytic uremic syndrome (HUS) and healthy controls. They discovered evidence of kallikrein-kinin system activation in some children with HUS, and this activation was associated with the extent of red blood cell fragmentation and kidney involvement. Preventing activation using a drug called C1-inhibitor, which inhibits the kallikrein-kinin system, confirmed the researchers' findings experimentally.

While the study focused on HUS, hemolysis occurs in many other diseases and clinical situations, including malaria. The researchers suggest that understanding this mechanism could provide insights into how red blood cell breakdown contributes to inflammation and disease in various conditions.