Airway diseases often feature persistent neutrophilic inflammation and infection. In cystic fibrosis bronchitis, for example, Pseudomonas aeruginosa is isolated frequently. Previously, this laboratory revealed that neutrophils become major sources of histamine in mice with tracheobronchitis caused by the wall-less bacterium Mycoplasma pulmonis . To test the hypothesis that more-broadly pathogenic P. aeruginosa (which expresses cell wall-associated LPS and novel toxins) has similar effects, we incubated naïve mouse neutrophils with two strains of P. aeruginosa . Strain PAO1 greatly increased neutrophil histamine content and secretion, whereas strain PA103 depressed histamine production by killing neutrophils. The histamine-stimulating capacity of PAO1, but not PA103-mediated toxicity, persisted in heat-killed organisms. In PAO1-infected mice, lung and neutrophil histamine content increased. However, PAO1 did not alter production by mast cells (classical histamine reservoirs), which also resisted PA103 toxicity. To explore mechanisms of neutrophil-selective induction, we measured changes in mRNA encoding histidine decarboxylase (rate-limiting for histamine synthesis), probed involvement of endotoxin-TLR pathways in Myd88 -deficient neutrophils, and examined contributions of pyocyanin and exotoxins. Results revealed that PAO1 increased histamine production by up-regulating histidine decarboxylase mRNA via pathways largely independent of TLR, pyocyanin, and type III secretion system exotoxins. PAO1 also increased histidine decarboxylase mRNA in neutrophils purified from infected lung. Stimulation required direct contact with neutrophils and was blocked by phagocytosis inhibitor cytochalasin D. In summary, Pseudomonas -augmented histamine production by neutrophils is strain-dependent in vitro and likely mediated by up-regulation of histidine decarboxylase. These findings raise the possibility that Pseudomonas -stimulated neutrophils can enhance airway inflammation by producing histamine. mast cell histidine decarboxylase Toll-like receptor endotoxin Myd88 exotoxin Footnotes BALF BAL fluid BMCMC bone marrow-derived cultured mast cell C t cycle threshold ExoA/S/T/U/Y exotoxin A/S/T/U/Y HDC histidine carboxylase HGPRT hypoxanthine guanine phosphoribosyl transferase LT leukotriene Mac-1 macrophage antigen 1 Received July 17, 2011. Revision received October 10, 2011. Accepted October 11, 2011. © 2012 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print November 10, 2011 , doi: 10.1189/jlb.0711356 February 2012 Journal of Leukocyte Biology vol. 91 no. 2 275-284 » Abstract Full Text Full Text (PDF) All Versions of this Article: jlb.0711356v1 91/2/275 most recent Classifications Inflammation, Extracellular Mediators, & Effector Molecules Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Xu, X. Articles by Caughey, G. H. PubMed PubMed citation Articles by Xu, X. Articles by Caughey, G. H. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 91 (2) From the Cover Editorials: Tim-3 puts on the brakes. Editorials: T cell memory, bone marrow, and aging: the good news. Spotlight on Leading Edge Research: Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes. Spotlight on Leading Edge Research: The impact of aging on memory T cell phenotype and function in the human bone marrow. Reviews: Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. Reviews: Non-human primate dendritic cells. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2012 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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