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Am J Physiol Heart Circ Physiol (April 11, 2002). doi:10.1152/ajpheart.00740.2001
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Articles in PresS, published online ahead of print April 11, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00740.2001
Submitted on August 17, 2001
Accepted on April 1, 2002

Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role

Rina Takamiya1, Makoto Murakami2, Mayumi Kajimura3, Nobuhito Goda3, Nobuya Makino3, Yoshihiro Takamiya3, Tokio Yamaguchi4, Yuzuru Ishimura3, Nobumichi Hozumi1, and Makoto Suematsu3*

1 Biotechnology, Science University of Tokyo, Noda City, Japan
2 Health Chemistry, Showa University, Tokyo, Japan
3 Biochemistry and Integrative Medical Biology, Keio University School of Medicine, Tokyo, Japan
4 Biochemical Genetics, Tokyo Medical and Dental University, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: msuem{at}sc.itc.keio.ac.jp.

This study aimed to examine 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, evoked a marked induction of the enzyme in MCs. Intravital videomicroscopy revealed that hemin pretreatment attenuated compound48/80-elicited degranulation of MCs and resultant leukocyte adhesion in venules. Superfusion with biliverdin or bilirubin but not that with CO, another reaction product of HO, mimicked suppressive actions of the HO-1 induction on both the cell degranulation and leukocyte adhesion elicited by the stimulus, suggesting requirement of the enzyme reaction to generate bilirubin in the inhibitory mechanisms. Such MC-desensitizing actions of bilirubin were observed in primary-cultured mast cells, 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 mastcytoma cell line RBL2H3. These results suggest that bilirubin generated through HO-1 serves as an anti-inflammatory substance which desensitizes mast cells and ameliorates leukocyte recruitment.




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