Hemopexin (Hx) is a plasma
glycoprotein mainly expressed in liver and, less abundantly, in the central and peripheral nervous systems. Hx has a high binding affinity with
heme and is considered to be a major transport vehicle of
heme into the liver, thus preventing both
heme-catalyzed oxidative damage and
heme-bound
iron loss. To determine the physiologic relevance of
heme-Hx complex formation, Hx-deficient mice were generated by homologous recombination in embryonic stem (ES) cells. The Hx-deficient mice were viable and fertile. Their plasma
iron level and blood parameters were comparable to those of control mice and they showed no evidence of tissue lesions caused by oxidative damage or abnormal
iron deposits. Moreover, they were sensitive to acute
hemolysis, as are wild-type mice. Nevertheless, Hx-null mice recovered more slowly after
hemolysis and were seen to have more severe renal damage than controls. After hemolytic stimulus, Hx-deficient mice presented prolonged
hemoglobinuria with a higher kidney
iron load and higher lipid peroxidation than control mice. Moreover, Hx-null mice showed altered posthemolysis
haptoglobin (Hp) turnover in as much as Hp persisted in the circulation after hemolytic stimulus. These data indicate that, although Hx is not crucial either for
iron metabolism or as a protection against oxidative stress under physiologic conditions, it does play an important protective role after hemolytic processes.