Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role
1 Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, Tokyo 160-8582; 2 Department of Biotechnology, Research Institute for Biological Sciences, Science University of Tokyo, Chiba 278-0022; 3 Department of Health Chemistry, School of Pharmaceutical Sci...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 283; no. 3; pp. H861 - H870 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.09.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Biochemistry and Integrative Medical
Biology, School of Medicine, Keio University, Tokyo 160-8582;
2 Department of Biotechnology, Research Institute for
Biological Sciences, Science University of Tokyo, Chiba 278-0022;
3 Department of Health Chemistry, School of
Pharmaceutical Sciences, Showa University, Tokyo 142-8555; and
4 Department of Biochemical Genetics, Medical
Research Institute, Tokyo Medical and Dental University, Tokyo
113-8549, Japan
This study examined the role of bilirubin
in heme oxygenase (HO)-1-mediated amelioration of mast cell
(MC)-elicited inflammatory responses. Pretreatment of rats with an
intraperitoneal injection of hemin, an inducer of HO-1, evolved a
marked induction of the enzyme in MCs. Intravital videomicroscopy
revealed that hemin pretreatment attenuated compound 48/80-elicited
degranulation of MCs and resultant leukocyte adhesion in venules.
Superfusion with biliverdin or bilirubin, but not with carbon monoxide
(CO), another product of the HO reaction, mimicked suppressive actions of the HO-1 induction on both the cell degranulation and leukocyte adhesion elicited by the stimulus, suggesting a requirement of the
enzyme reaction to generate bilirubin in the inhibitory mechanisms. Such MC-desensitizing actions of bilirubin were observed in
primary-cultured MCs and reproduced irrespective of the choice of
stimuli, such as compound 48/80, calcium ionophore, and anti-IgE serum.
Furthermore, MC-stabilizing effects of HO-1 were reproduced by the gene
transfection of the enzyme into mastocytoma cell line RBL2H3. These
results suggest that bilirubin generated through HO-1 serves as an
anti-inflammatory substance that desensitizes MCs and ameliorates
leukocyte recruitment.
inflammation; bilirubin; biliverdin; leukocyte adhesion |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00740.2001 |