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Abstract

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses. Because ferritin synthesis is stimulated by Fe 2+ , which is a product of heme degradation, we examined the relation between HO-1 and ferritin levels in the serum of patients with hemophagocytic syndrome (HPS), adultonset Still's disease (ASD), and other diseases that may cause hyperferritinemia. Seven patients with HPS, 10 with ASD, 73 with other rheumatic diseases, 20 with liver diseases, 10 recipients of repeated blood transfusion because of hematological disorders, and 22 healthy volunteers were enrolled. Serum HO-1 and ferritin levels were determined by ELISA. Expression of HO-1 mRNA and protein by peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR and immunocytochemical techniques, respectively. Serum levels of HO-1 were significantly higher in patients with active HPS and ASD than in the other groups (P < 0.01). HO-1 levels were not elevated in patients with other causes of hyperferritinemia but were moderately elevated in patients with dermatomyositis/polymyositis. Among patients with HPS and ASD, serum HO-1 levels correlated closely with serum ferritin levels, and the levels of both returned to normal after therapy had induced remission. Increased expression of HO-1 mRNA was confirmed in PBMCs from some patients with HPS and ASD. Hyperferritinemia correlated closely with increased serum HO-1 in patients with HPS and ASD but not other conditions, indicating that measurement of serum HO-1 and ferritin levels would be useful in the differential diagnosis of hyperferritinemia and perhaps also in monitoring disease activity in HPS and ASD.

Heme Oxygenase-1 Promotes the Persistence ofLeishmania chagasiInfection

“…Our data shows that high concentrations of serum HO-1 are associated with a higher chance to have VL in our cohort of patients. Consistently with our results, increased concentrations of HO-1 have already been associated with other diseases such as vasculitis in Henoch-Schonlein purpura (63), hemophagocytic syndromes from hematological conditions (64, 65), type 2 diabetes (66) and prostate cancer (67). Thus, while showing strong associations between HO-1 and VL, our study expands the list of the diseases in which HO-1 potentially plays fundamental role.…”

Chronic Murine Typhoid Fever Is a Natural Model of Secondary Hemophagocytic Lymphohistiocytosis

“…Erythrophagocytic macrophages have been shown to express heme-oxygenase 1 (HO-1) in human sepsis cases [41], and inhibit pro-inflammatory cytokine production in cultured mouse bone marrow cells (Slc11a1/Nramp1 +/+ ) [42], thereby suggesting an anti-inflammatory role. Increased serum HO-1 also occurs in cases of sHLH in correlation with hyperferritinemia [43]. Whether HO-1 facilitates S .…”

ELISA Development for Serum Hemeoxygenase-1 and Its Application to Patients with Acute Respiratory Distress Syndrome

“…Its expression in lung tissue was reported to increase in patients with diffuse alveolar damage (DAD), desquamative interstitial pneumonia, pulmonary sarcoidosis, and silicosis, whereas its expression decreased in patients with usual interstitial pneumonia (UIP) and chronic pulmonary obstructive disease (COPD) [ 5 – 9 ]. Peripheral blood HO-1 measured by enzyme-linked immunosorbent assay (ELISA) was reported to be useful in monitoring disease activity in patients with hemophagocytic syndrome and adult-onset Still's disease and is a predictor of lung function decline in patients with silicosis [ 10 , 11 ]. However, there is no commercial detection kit to accurately measure serum HO-1 because the previously used kit was designed to measure HO-1 in cell lysates and tissue extracts and can be affected by factors contained in serum [ 11 ].…”