Abstract
Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.
Highlights
Heme is a major component of hemoglobin (Hb), and is a product of erythrocyte destruction
The patient’s serum reveals inclusion of large amounts of both OxyHb and methemoglobin (MetHb) (C). These results indicated that either massive hemolysis was constantly taking place in vivo or that Hb was accumulating in serum due to defects in the Hb catabolic pathway
After we reported the first case of human Heme oxygenase (HO)-1 deficiency, 5 cases from India were confirmed by HO-1 gene analysis (Radhakrishnan 2011 [19], Radhakrishnan 2011 [20], Gupta 2016 [21], and personal communications)
Summary
Heme is a major component of hemoglobin (Hb), and is a product of erythrocyte destruction. Chronic infantile neurological cutaneous and articular syndrome (alternatively calledThe ne- combination of fever, erythematous rash, and joint pain suggested that the patient from a onatal-onset multisystem inflammatory disease) The latter condition is known suffered as childhood chronic inflammatory illness such as systemic juvenile idiopathic arthritis cryopyrin-associated periodic syndrome. Furmg/dL, normal range; 40–180 mg/dL) and a large amount of Hb-Hp complex was detected ther study revealed that serum Hp concentration was extremely elevated These data suggested that the Hb-Hp complex was normal range; 40–180 mg/dL) and a large amount of Hb-Hp complex was detected in a somehow bypassing the normal scavenger system and overflowing into urine. We could not see whether circulating monocytes from the patient expressed Hb-Hp receptor CD163, no expression was detectable on Kupffer cells from the liver of the patient [27]
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