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Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation.
Int Immunol. 2005 Feb; 17(2):155-65.II

Abstract

Monocyte activation, apoptosis and differentiation are hallmarks of most inflammatory vascular disorders. We studied the effects of heme oxygenase-1 (HO-1) induced by its substrate hemin on apoptosis, caspase-3 expression and the differentiation of freshly isolated human monocytes. Hemin induced HO-1 in a dose- and time-dependent fashion as measured by semi-quantitative RT-PCR and flow cytometry. Apoptosis was markedly suppressed by hemin in cells rendered apoptotic by serum deprivation or dexamethasone as determined by flow cytometric detection of annexin V binding or transmission electron microscopy (TEM). The specific HO-1 inhibitor zinc protoporphyrin (ZnPP) reversed the effects of hemin on monocyte apoptosis and diminished cell lifespan. Surprisingly, the cytoprotective effects of hemin were positively correlated with caspase-3 up-regulation. Hemin-induced apoptosis suppression was enhanced by the caspase-3 inhibitor DEVD-CHO, indicating that caspase-3 was active in a pro-apoptotic fashion. Hemin inhibited CD95 as a putative cytoprotective mechanism. Morphological studies and detection of CD86 showed that monocytes differentiated into macrophages in response to hemin after relatively long incubation times, a phenomenon that might be provoked by caspase-3-regulated pathways. Our results confirm a similar cytoprotective effect of hemin/HO-1 for monocytes as has been shown for other cells, despite caspase-3 up-regulation. The fact that HO-1 may adversely affect monocyte survival and differentiation could be of particular significance in future therapies for occlusive vascular diseases or transplant rejection.

Authors+Show Affiliations

Lang D
Department of Medicine D, University of Muenster, Germany. langd@uni-muenster.de
Reuter S
No affiliation info available
Buzescu T
No affiliation info available
August C
No affiliation info available
Heidenreich S
No affiliation info available

MeSH

Antigens, CDApoptosisB7-2 AntigenCaspase 3CaspasesCells, CulturedHeme Oxygenase (Decyclizing)Heme Oxygenase-1HeminHumansMembrane GlycoproteinsMembrane ProteinsMonocytesProto-Oncogene Proteins c-bcl-2Up-Regulationfas Receptor

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15611319

Citation

Lang, Detlef, et al. "Heme-induced Heme Oxygenase-1 (HO-1) in Human Monocytes Inhibits Apoptosis Despite Caspase-3 Up-regulation." International Immunology, vol. 17, no. 2, 2005, pp. 155-65.
Lang D, Reuter S, Buzescu T, et al. Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation. Int Immunol. 2005;17(2):155-65.
Lang, D., Reuter, S., Buzescu, T., August, C., & Heidenreich, S. (2005). Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation. International Immunology, 17(2), 155-65.
Lang D, et al. Heme-induced Heme Oxygenase-1 (HO-1) in Human Monocytes Inhibits Apoptosis Despite Caspase-3 Up-regulation. Int Immunol. 2005;17(2):155-65. PubMed PMID: 15611319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation. AU - Lang,Detlef, AU - Reuter,Stefan, AU - Buzescu,Tania, AU - August,Christian, AU - Heidenreich,Stefan, Y1 - 2004/12/20/ PY - 2004/12/22/pubmed PY - 2005/6/15/medline PY - 2004/12/22/entrez SP - 155 EP - 65 JF - International immunology JO - Int Immunol VL - 17 IS - 2 N2 - Monocyte activation, apoptosis and differentiation are hallmarks of most inflammatory vascular disorders. We studied the effects of heme oxygenase-1 (HO-1) induced by its substrate hemin on apoptosis, caspase-3 expression and the differentiation of freshly isolated human monocytes. Hemin induced HO-1 in a dose- and time-dependent fashion as measured by semi-quantitative RT-PCR and flow cytometry. Apoptosis was markedly suppressed by hemin in cells rendered apoptotic by serum deprivation or dexamethasone as determined by flow cytometric detection of annexin V binding or transmission electron microscopy (TEM). The specific HO-1 inhibitor zinc protoporphyrin (ZnPP) reversed the effects of hemin on monocyte apoptosis and diminished cell lifespan. Surprisingly, the cytoprotective effects of hemin were positively correlated with caspase-3 up-regulation. Hemin-induced apoptosis suppression was enhanced by the caspase-3 inhibitor DEVD-CHO, indicating that caspase-3 was active in a pro-apoptotic fashion. Hemin inhibited CD95 as a putative cytoprotective mechanism. Morphological studies and detection of CD86 showed that monocytes differentiated into macrophages in response to hemin after relatively long incubation times, a phenomenon that might be provoked by caspase-3-regulated pathways. Our results confirm a similar cytoprotective effect of hemin/HO-1 for monocytes as has been shown for other cells, despite caspase-3 up-regulation. The fact that HO-1 may adversely affect monocyte survival and differentiation could be of particular significance in future therapies for occlusive vascular diseases or transplant rejection. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/15611319/Heme_induced_heme_oxygenase_1__HO_1__in_human_monocytes_inhibits_apoptosis_despite_caspase_3_up_regulation_ DB - PRIME DP - Unbound Medicine ER -