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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5205-5214. Prepublished online as a Blood First Edition Paper on February 12, 2008; DOI 10.1182/blood-2007-09-113902. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-113902v1 111/10/5205    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kiefmann, R. Articles by Bhattacharya, J. Search for Related Content PubMed PubMed Citation Articles by Kiefmann, R. Articles by Bhattacharya, J. Related Collections Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Red blood cells induce hypoxic lung inflammation Rainer Kiefmann1, Joseph M. Rifkind2, Enika Nagababu2, and Jahar Bhattacharya1 1 Lung Biology Laboratory, College of Physicians & Surgeons, Columbia University, St Luke's Roosevelt Hospital Center, New York, NY; and 2 Molecular Dynamics Section, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD Hypoxia, which commonly associates with respiratory and cardiovascular diseases, provokes an acute inflammatory response. However, underlying mechanisms are not well understood. Here we report that red blood cells (RBCs) induce hypoxic inflammation by producing reactive oxygen species (ROS) that diffuse to endothelial cells of adjoining blood vessels. Real-time fluorescence imaging of rat and mouse lungs revealed that in the presence of RBC-containing vascular perfusion, hypoxia increased microvascular ROS, and cytosolic Ca2+, leading to P-selectin–dependent leukocyte recruitment. However, in the presence of RBC-free perfusion, all hypoxia-induced responses were completely inhibited. Because hemoglobin (Hb) autoxidation causes RBC superoxide formation that readily dismutates to H2O2, hypoxia-induced responses were lost when we inhibited Hb autoxidation with CO or nitrite, or when the H2O2 inhibitor, catalase was added to the infusion to neutralize the RBC-derived ROS. By contrast, perfusion with RBCs from BERK-trait mice that are more susceptible to Hb autoxidation and to hypoxia-induced superoxide production enhanced the hypoxia-induced responses. We conclude that in hypoxia, increased Hb autoxidation augments superoxide production in RBCs. Consequently, RBCs release H2O2 that diffuses to the lung microvascular endothelium, thereby initiating Ca2+-dependent leukocyte recruitment. These findings are the first evidence that RBCs contribute to hypoxia-induced inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hypoxic erythrocytes spark lung leukocyte adhesion Guy A. Zimmerman Blood 2008 111: 4831-4832. [Full Text] [PDF] This article has been cited by other articles: R. Zennadi, A. Chien, K. Xu, M. Batchvarova, and M. J. Telen Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium Blood, October 15, 2008; 112(8): 3474 - 3483. [Abstract] [Full Text] [PDF]

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