Heme oxygenase-1 expression in murine dendritic cell subpopulations: effect on CD8+ dendritic cell differentiation in vivo.
Heme oxygenase-1 (HO-1) is a microsomal enzyme with antioxidant, antiapoptotic, and immunoregulatory functions. We studied the expression of HO-1 by bone marrow-derived dendritic cells (BMDCs) and splenic DC subpopulations under quiescent conditions or following lipopolysaccharide (LPS) stimulation. The kinetics of HO-1 expression by BMDCs depended on the conditions under which they were propagated. Expression of HO-1 in mouse BMDCs in 100 U/ml GM-CSF peaked at 16 hours after LPS treatment and maintained expression for at least 48 hours. But cultures in 800 U/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) showed peak expression by 16 hours that disappeared by 48 hours after LPS stimulation, similar to BMDCs cultured in both 100 U/ml GM-CSF and IL-4 (10 ng/ml). By flow cytometry, a large proportion of CD8(+) splenic DCs strongly expressed HO-1, and this population significantly increased following LPS administration in vivo. In HO-1(-/-) mice, the proportion of splenic CD8(+) DCs was significantly decreased in comparison with HO-1(+/+) mice. In addition, a unique subpopulation of MHC II(-)CD11b(+)CD11c(+) cells was prominent in HO-1(-/-) spleens. Injection of GFP-labeled HO-1(+/+) splenic DC precursors into HO-1(+/+) mice resulted in the generation of GFP(+)CD8(+) DCs in the spleen after 5 days, but GFP(+) CD8(+) DCs failed to appear in HO-1(-/-) spleens. Conversely, GFP(+)HO-1(-/-) splenic cells also generated GFP(+)CD8(+) DCs in HO-1(+/+) mice. These results show that HO-1 is involved in splenic DC differentiation, and/or the homing of CD8(+) splenic DC precursors appears to be dependent on HO-1 expression by the host.
Park
Dong Jun
DJ
Department of Medicine, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Agarwal
Anupam
A
George
James F
JF
D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000502:physiology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013234:Stem Cells / Q000502:physiology
D016827:CD8 Antigens; D008070:Lipopolysaccharides; D051547:Heme Oxygenase-1
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