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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5187-5194. Prepublished online as a Blood First Edition Paper on February 15, 2008; DOI 10.1182/blood-2007-10-117283. This Article Full Text (PDF) All Versions of this Article: blood-2007-10-117283v1 111/10/5187    most recent Alert me when this article is cited Alert me if a correction is posted 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 Morton, J. Articles by O'Donnell, V. B. Search for Related Content PubMed PubMed Citation Articles by Morton, J. Articles by O'Donnell, V. B. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 10, 2007 Accepted February 12, 2008 Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFN-dependent iNOS expression in the vasculature of healthy mice Jonathan Morton, Barbara Coles, Kate Wright, Awen Gallimore, Jason D Morrow, Erin S Terry, Peter B Anning, B. Paul Morgan, Vincent Dioszeghy, Hartmut Kuhn, Pavlos Chaitidis, Adrian J. Hobbs, Simon A Jones, and Valerie B. O'Donnell* Dept of Medical Biochemistry and Immunology, Cardiff University, Cardiff, United Kingdom Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, United States Institute of Biochemistry, University Medicine Berlin-Charite, Berlin, Germany Wolfson Institute for Biomedical Research, University College London, London, United Kingdom * Corresponding author; email: o-donnellvb{at}cardiff.ac.uk. Whether leukocytes exert an influence on vascular function in vivo is not known. Here, genetic and pharmacologic approaches show that the absence of neutrophils leads to acute blood pressure dysregulation. Following neutrophil depletion, systolic blood pressure falls significantly over 3 days (88.0 ± 3.5 vs 104.0 ± 2.8 mmHg, day 3 vs day 0, mean ± SEM, p < 0.001), and aortic rings from neutropenic mice do not constrict properly. The constriction defect is corrected using L-NAME or the specific iNOS inhibitor 1400W, while acetylcholine relaxation is normal. iNOS or IFN deficient mice are protected from neutropenia-induced hypotension, indicating that iNOS-derived NO is responsible and that its induction involves IFN. Oral enrofloxacin partially inhibited hypotension, implicating bacterial products. Roles for cyclooxygenase, complement C5 or endotoxin were excluded, although urinary prostacyclin metabolites were elevated. Neutrophil depletion required complement opsinization, with no evidence for intravascular degranulation. In summary, circulating neutrophils contribute to maintaining physiological tone in the vasculature, at least in part through suppressing early pro-inflammatory effects of infection. The speed with which hypotension developed provides insight into early changes that occur in the absence of neutrophils and illustrates the importance of constant surveillance of mucosal sites by granulocytes in healthy mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Blood pressure regulation: role for neutrophils? Volker Rudolph, Tanja K. Rudolph, and Bruce A. Freeman Blood 2008 111: 4840. [Full Text] [PDF] This article has been cited by other articles: K. B. Abbitt, M. J. Cotter, V. C. Ridger, D. C. Crossman, P. G. Hellewell, and K. E. Norman Antibody ligation of murine Ly-6G induces neutropenia, blood flow cessation, and death via complement-dependent and independent mechanisms J. Leukoc. Biol., January 1, 2009; 85(1): 55 - 63. [Abstract] [Full Text] [PDF]

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