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Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFN -dependent iNOS expression in the vasculature of healthy mice

Morton, Jonathan, Coles, Barbara, Wright, Kate Louise, Gallimore, Awen Myfanwy, Morrow, Jason D., Terry, Erin S., Anning, Peter, Morgan, Bryan Paul, Dioszeghy, Vincent, Kuhn, Hartmut, Chaitidis, Pavlos, Hobbs, Adrian J., Jones, Simon Arnett and O'Donnell, Valerie Bridget 2008. Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFN -dependent iNOS expression in the vasculature of healthy mice. Blood 111 (10) , pp. 5187-5194. 10.1182/blood-2007-10-117283

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Abstract

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 mm Hg, day 3 vs day 0, mean ± SEM, P < .001), and aortic rings from neutropenic mice do not constrict properly. The constriction defect is corrected using l-nitroarginine-methyl ester (L-NAME) or the specific inducible nitric oxide synthase (iNOS) inhibitor 1400W, while acetylcholine relaxation is normal. iNOS- or IFNγ-deficient mice are protected from neutropenia-induced hypotension, indicating that iNOS-derived nitric oxide (NO) is responsible and that its induction involves IFNγ. 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 proinflammatory 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine
R Medicine > RS Pharmacy and materia medica
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 09 Jan 2018 19:56
URI: http://orca.cf.ac.uk/id/eprint/28008

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