title: Heme oxygenase-1 expression in murine dendritic cell subpopulations: effect on CD8+ dendritic cell differentiation in vivo.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Park
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: James F
authors.initials: JF
authors.lastname: George
mesh_terms: 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
chemical_list: D016827:CD8 Antigens; D008070:Lipopolysaccharides; D051547:Heme Oxygenase-1
references.citation: J Clin Invest. 1999 Jan;103(1):129-35
references.pmid: 9884342
references.citation: J Immunol. 1996 Apr 15;156(8):2918-26
references.pmid: 8609412
references.citation: Proc Natl Acad Sci U S A. 1968 Oct;61(2):748-55
references.pmid: 4386763
references.citation: Free Radic Biol Med. 2004 Oct 15;37(8):1097-104
references.pmid: 15451051
references.citation: Mol Nutr Food Res. 2005 Nov;49(11):1030-43
references.pmid: 16208635
references.citation: Blood. 2003 Sep 15;102(6):2187-94
references.pmid: 12791652
references.citation: Pediatr Transplant. 2007 Dec;11(8):850-9
references.pmid: 17976119
references.citation: Front Biosci. 2007 Sep 01;12:4932-45
references.pmid: 17569621
references.citation: Am J Pathol. 2004 Sep;165(3):1045-53
references.pmid: 15331427
references.citation: J Immunol. 2004 Jan 15;172(2):1018-27
references.pmid: 14707075
references.citation: J Immunol. 2001 Jul 15;167(2):741-8
references.pmid: 11441078
references.citation: J Immunol. 2009 Feb 15;182(4):1877-84
references.pmid: 19201840
references.citation: Am J Pathol. 2008 Jul;173(1):154-60
references.pmid: 18511516
references.citation: Antioxid Redox Signal. 2007 Dec;9(12):2049-63
references.pmid: 17854277
references.citation: J Immunol. 2001 Mar 15;166(6):4185-94
references.pmid: 11238670
references.citation: Pediatr Int. 2007 Apr;49(2):125-32
references.pmid: 17445026
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10925-30
references.pmid: 9380736
references.citation: Nat Immunol. 2006 Jun;7(6):663-71
references.pmid: 16680143
references.citation: J Am Soc Nephrol. 2007 Feb;18(2):414-20
references.pmid: 17229906
references.citation: J Exp Med. 1996 Jan 1;183(1):317-22
references.pmid: 8551239
references.citation: Wien Klin Wochenschr. 2002;114 Suppl 4:1-3
references.pmid: 15499991
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: Blood. 2005 Sep 1;106(5):1694-702
references.pmid: 15920011
references.citation: Hum Immunol. 2006 Jun;67(6):430-2
references.pmid: 16728265
references.citation: J Immunol. 2008 Jun 15;180(12):7919-30
references.pmid: 18523255
references.citation: Biochem Biophys Res Commun. 2005 Dec 9;338(1):568-77
references.pmid: 16183036
references.citation: Nat Immunol. 2007 Nov;8(11):1217-26
references.pmid: 17922015
references.citation: Methods Mol Biol. 2008;415:163-78
references.pmid: 18370154
references.citation: J Immunol Methods. 2002 Apr 1;262(1-2):145-57
references.pmid: 11983228
references.citation: Blood. 2003 Jul 15;102(2):601-4
references.pmid: 12649155
references.citation: Pharmacol Rev. 2008 Mar;60(1):79-127
references.pmid: 18323402
references.citation: Am J Pathol. 2000 May;156(5):1527-35
references.pmid: 10793064
references.citation: Transplant Proc. 2005 Oct;37(8):3463-7
references.pmid: 16298630
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10919-24
references.pmid: 9380735
references.citation: Cell Immunol. 2001 Dec 15;214(2):110-22
references.pmid: 12088410
references.citation: Am J Kidney Dis. 2000 May;35(5):863-70
references.pmid: 10793020
references.citation: Blood. 2001 Sep 1;98(5):1512-23
references.pmid: 11520802
references.citation: Exp Dermatol. 2007 Aug;16(8):661-70
references.pmid: 17620093
references.citation: Nat Med. 1998 Sep;4(9):1073-7
references.pmid: 9734404
references.citation: Nat Rev Immunol. 2007 Jan;7(1):19-30
references.pmid: 17170756
references.citation: Am J Physiol Renal Physiol. 2000 May;278(5):F726-36
references.pmid: 10807584
references.citation: J Immunol. 2000 Mar 15;164(6):2978-86
references.pmid: 10706685
references.citation: FASEB J. 2006 Apr;20(6):776-8
references.pmid: 16473885
references.citation: Kidney Int. 2001 Jan;59(1):106-17
references.pmid: 11135063
references.citation: Kidney Int. 1995 Oct;48(4):1298-307
references.pmid: 8569092