Allergic and Immunological Disorders

Abstract

The immune system provides effective defense mechanisms to protect hosts from various pathogens and toxic compounds. However, these immunological functions themselves become oxidative stress to hosts. Heme oxygenase (HO) plays a central role in heme metabolism. HO protects cells and organs from injury evoked by various oxidative stresses. A detailed analysis of the first human case of HO-1 deficiency revealed that this enzyme is involved in the protection of multiple tissues and organs. Notably, in vivo studies have shown localized HO-1 production to select cell types, e.g., renal tubular epithelium, hepatic Kupffer cells, vascular endothelium and monocytes/macrophages. In vivo and in vitro studies indicated that sustained HO-1 deficiency results in progressive monocyte dysfunction, unregulated macrophage activation, and endothelial cell dysfunction, leading to a catastrophic systemic inflammatory response syndrome. In addition to conventional immunosuppressive and anti-inflammatory therapies, the novel therapy to induce HO-1 production by pharmacological intervention is promising.