Significance of haptoglobin and hemopexin in Shiga toxin-mediated HUS
New paper published on the role of haptoglobin and hemopexin in the development of Shiga toxin-induced hemolytic uremic syndrome (HUS)
Hemolytic uremic syndrome (HUS) is a renal disease that can be caused by infection with Shiga toxin-producing Escherichia coli (STEC) and is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Shiga toxin (Stx) represents one of the main virulence factors of these microorganisms. The effects of Stx include initialization of hemolysis followed by increased hemoglobin accumulation. This process releases heme, which can cause organ damage in life-threatening infections even at low levels of systemic hemolysis.
Members of the NWG Translational Septomics (Head: Prof. Dr. med. Sina M. Coldewey, PhD) in cooperation with the research groups of Prof. Kerstin Amann and Christoph Daniel (Erlangen, Germany), Prof. Florian Gunzer (Dresden, Germany), Prof. Emanuela Tolosano (Turin, Italy) and Prof. Stefan H. Heinemann (Jena, Germany) have investigated in a murine model of HUS whether haptoglobin and hemopexin play a role in Shiga toxin-mediated HUS. Haptoglobin and hemopexin are plasma proteins that play an important function in heme and iron homeostasis. As acute phase proteins, they are also involved in inflammatory processes and can protect tissues from oxidative stress.
The researchers conclude that haptoglobin and hemopexin play different roles in the development of Stx-mediated HUS. While haptoglobin has been shown to be involved, hemopexin does not appear to be important in the resolution of Stx-induced injury, such as neutrophil recruitment and platelet deposition in the kidney.
The results were published in the journal Kidney International.
Pirschel W, Mestekemper AN, Wissuwa B, Krieg N, Kröller S, Daniel C, Gunzer F, Tolosano E, Bauer M, Amann K, Heinemann SH, Coldewey SM (2022) Divergent roles of haptoglobin and hemopexin deficiency for disease progression of Shiga-toxin-induced hemolytic-uremic syndrome in mice. Kidney Int. S0085-2538(22)00016-3, doi: 10.1016/j.kint.2021.12.024