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Am J Physiol Heart Circ Physiol 283: H861-H870, 2002. First published April 11, 2002; doi:10.1152/ajpheart.00740.2001
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Vol. 283, Issue 3, H861-H870, September 2002

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

Rina Takamiya2, Makoto Murakami3, Mayumi Kajimura1, Nobuhito Goda1, Nobuya Makino1, Yoshihiro Takamiya1, Tokio Yamaguchi4, Yuzuru Ishimura1, Nobumichi Hozumi2, and Makoto Suematsu1

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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