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Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2001, Vol. 98, No. 6, pp. 1802-1811 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase Frank A. D. T. G. Wagener, Andreas Eggert, Otto C. Boerman, Wim J. G. Oyen, Albert Verhofstad, Nader G. Abraham, Gosse Adema, Yvette van Kooyk, Theo de Witte, and Carl G. Figdor From the Departments of Tumor Immunology, Nuclear Medicine, Pathology, and Hematology, University Medical Center Nijmegen, The Netherlands, and the Department of Pharmacology, New York Medical College, Valhalla. Various pathologic conditions, such as hemorrhage, hemolysis and cell injury, are characterized by the release of large amounts of heme. Recently, it was demonstrated that heme oxygenase (HO), the heme-degrading enzyme, and heme are able to modulate adhesion molecule expression in vitro. In the present study, the effects of heme and HO on inflammation in mice were analyzed by monitoring the biodistribution of radiolabeled liposomes and leukocytes in conjunction with immunohistochemistry. Small liposomes accumulate in inflamed tissues by diffusion because of locally enhanced vascular permeability, whereas leukocytes actively migrate into inflammatory areas through specific adhesive interactions with the endothelium and chemotaxis. Exposure to heme resulted in a dramatic increase in liposome accumulation in the pancreas, but also intestines, liver, and spleen exhibited significantly increased vascular permeability. Similarly, intravenously administered heme caused an enhanced influx of radiolabeled leukocytes into these organs. Immunohistochemical analysis showed differential up-regulation of the adhesion molecules ICAM-1, P-selectin, and fibronectin in liver and pancreas in heme-treated animals. Heme-induced adhesive properties were accompanied by a massive influx of granulocytes into these inflamed tissues, suggesting an important contribution to the pathogenesis of inflammatory processes. Moreover, inhibition of HO activity exacerbated heme-induced granulocyte infiltration. Here it is demonstrated for the first time that heme induces increased vascular permeability, adhesion molecule expression, and leukocyte recruitment in vivo, whereas HO antagonizes heme-induced inflammation possibly through the down-modulation of adhesion molecules. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. J. Woollard, S. Sturgeon, J. P. F. Chin-Dusting, H. H. Salem, and S. P. 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