Corticosteroid enhances heme oxygenase-1 production by circulating monocytes by up-regulating hemoglobin scavenger receptor and amplifying the receptor-mediated uptake of hemoglobin-haptoglobin complex.
This study examined the relationship between steroid treatment and CD163-mediated downstream pathways linked to inflammatory resolution. Twelve patients referred for congenital heart disease surgery were divided into two groups based on the severity of intravascular hemolysis during cardiopulmonary bypass surgery. Patients with severe intravascular hemolysis were administered haptoglobin during the procedure. Flow cytometry indicated a peak in monocyte CD163 expression on post-operative day 1 in both groups. Enhanced and prolonged heme oxygenase-1 (HO-1) mRNA expression levels were observed in patients who received haptoglobin. Binding of hemoglobin-haptoglobin complex (Hb/Hp) to CD163 resulted in significant induction of HO-1 by peripheral blood mononuclear cells after exposure to dexamethasone prior to culture. This effect was significantly inhibited by anti-CD163 antibody. Our results demonstrated up-regulation of CD163 expression on the monocyte surface by steroid treatment. Steroid treatment was suggested to facilitate CD163-mediated endocytosis of hemoglobin to monocytes/macrophages and thereby induce acceleration of HO-1 synthesis.
Yamazaki
Haruyuki
H
Department of Pediatrics, Angiogenesis and Vascular Development, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Japan.
Ohta
Kunio
K
Tsukiji
Hidenori
H
Toma
Tomoko
T
Hashida
Yoko
Y
Ishizaki
Akiko
A
Saito
Takekatsu
T
Arai
Sadahiko
S
Koizumi
Shoichi
S
Yachie
Akihiro
A
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006242:Haptoglobins / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000188:drug therapy / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000098902:CD163 Antigen
D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D051547:Heme Oxygenase-1