Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice

John D Belcher, Hemachandra Mahaseth, Thomas E. Welch, Leo E. Otterbein, Robert P Hebbel, Gregory M Vercellotti

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Transgenic sickle mice expressing βs hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-κB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-κB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-κB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.

Original languageEnglish (US)
Pages (from-to)808-816
Number of pages9
JournalJournal of Clinical Investigation
Volume116
Issue number3
DOIs
StatePublished - Mar 1 2006

Fingerprint

Heme Oxygenase-1
Transgenic Mice
Inflammation
Heme Oxygenase (Decyclizing)
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Blood Vessels
Hemoglobins
Biliverdine
Reticulocyte Count
Skin
Hemin
Haptoglobins
Vascular Endothelium
Carbon Monoxide
Heme
Bilirubin
Adenoviridae
Endothelium
Leukocytes

Cite this

Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. / Belcher, John D; Mahaseth, Hemachandra; Welch, Thomas E.; Otterbein, Leo E.; Hebbel, Robert P; Vercellotti, Gregory M.

In: Journal of Clinical Investigation, Vol. 116, No. 3, 01.03.2006, p. 808-816.

Research output: Contribution to journalArticle

@article{b6b65224badb4a91906f36f121e952ac,
title = "Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice",
abstract = "Transgenic sickle mice expressing βs hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-κB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-κB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-κB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.",
author = "Belcher, {John D} and Hemachandra Mahaseth and Welch, {Thomas E.} and Otterbein, {Leo E.} and Hebbel, {Robert P} and Vercellotti, {Gregory M}",
year = "2006",
month = "3",
day = "1",
doi = "10.1172/JCI26857",
language = "English (US)",
volume = "116",
pages = "808--816",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

TY - JOUR

T1 - Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice

AU - Belcher, John D

AU - Mahaseth, Hemachandra

AU - Welch, Thomas E.

AU - Otterbein, Leo E.

AU - Hebbel, Robert P

AU - Vercellotti, Gregory M

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Transgenic sickle mice expressing βs hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-κB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-κB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-κB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.

AB - Transgenic sickle mice expressing βs hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-κB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-κB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-κB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.

UR - http://www.scopus.com/inward/record.url?scp=33644649611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644649611&partnerID=8YFLogxK

U2 - 10.1172/JCI26857

DO - 10.1172/JCI26857

M3 - Article

VL - 116

SP - 808

EP - 816

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 3

ER -