title: Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa.
abstract: 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.
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Jeanine P
authors.initials: JP
authors.lastname: Wiener-Kronish
authors.forename: George H
authors.initials: GH
authors.lastname: Caughey
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000494:pharmacology; D018441:Biofilms; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006632:Histamine / Q000096:biosynthesis*; D006636:Histamine Release; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000502:physiology*; D011710:Pyocyanine / Q000494:pharmacology; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
chemical_list: D001427:Bacterial Toxins; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D006632:Histamine; D011710:Pyocyanine; D036002:ADP Ribose Transferases; C444820:exoenzyme S
references.citation: Mol Microbiol. 1997 Jun;24(6):1249-62
references.pmid: 9218773
references.citation: Am J Respir Crit Care Med. 2006 Jan 15;173(2):219-25
references.pmid: 16210667
references.citation: Microbiology (Reading). 2001 Oct;147(Pt 10):2659-2669
references.pmid: 11577145
references.citation: Thorax. 1996 Mar;51(3):267-71
references.pmid: 8779129
references.citation: J Bacteriol. 2008 Apr;190(8):2726-38
references.pmid: 18039770
references.citation: Am Rev Respir Dis. 1982 Nov;126(5):833-6
references.pmid: 6816110
references.citation: Am J Pathol. 2009 Dec;175(6):2473-88
references.pmid: 19893030
references.citation: Curr Opin Pharmacol. 2007 Jun;7(3):244-51
references.pmid: 17418640
references.citation: Eur J Immunol. 2004 May;34(5):1472-82
references.pmid: 15114681
references.citation: N Engl J Med. 2000 Jul 27;343(4):269-80
references.pmid: 10911010
references.citation: Infect Immun. 1997 Feb;65(2):579-86
references.pmid: 9009316
references.citation: Br Med J (Clin Res Ed). 1986 Mar 29;292(6524):857-8
references.pmid: 3083910
references.citation: Lancet. 1984 Aug 18;2(8399):372-4
references.pmid: 6147454
references.citation: Mol Microbiol. 1996 Dec;22(5):991-1003
references.pmid: 8971719
references.citation: Immunology. 2000 Apr;99(4):600-6
references.pmid: 10792508
references.citation: J Bacteriol. 1990 Feb;172(2):884-900
references.pmid: 2153661
references.citation: J Immunol. 2008 Mar 1;180(5):3502-11
references.pmid: 18292577
references.citation: Thorax. 1998 Mar;53(3):213-9
references.pmid: 9659359
references.citation: Clin Exp Allergy. 2005 Jan;35(1):82-8
references.pmid: 15649271
references.citation: J Bacteriol. 2007 Mar;189(6):2203-9
references.pmid: 17209027
references.citation: Pharmacol Ther. 2009 Oct;124(1):86-95
references.pmid: 19555716
references.citation: J Immunol. 2003 Aug 1;171(3):1319-27
references.pmid: 12874221
references.citation: Infect Immun. 1995 Jan;63(1):1-8
references.pmid: 7806344
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Curr Opin Pulm Med. 2009 Mar;15(2):138-42
references.pmid: 19532029
references.citation: J Clin Invest. 2002 Feb;109(3):317-25
references.pmid: 11827991
references.citation: Mol Microbiol. 1997 Aug;25(3):547-57
references.pmid: 9302017
references.citation: Leuk Res. 2003 Aug;27(8):677-82
references.pmid: 12801524
references.citation: Curr Opin Microbiol. 2009 Feb;12(1):61-6
references.pmid: 19168385
references.citation: Chest. 2000 May;117(5 Suppl 2):380S-5S
references.pmid: 10843981
references.citation: Nature. 2000 Oct 12;407(6805):762-4
references.pmid: 11048725
references.citation: Chest. 2001 Jan;119(1):105-14
references.pmid: 11157591
references.citation: J Exp Med. 2006 Dec 25;203(13):2907-17
references.pmid: 17158962
references.citation: Br J Dis Chest. 1987 Jul;81(3):260-7
references.pmid: 2959308
references.citation: Burns. 2005 Mar;31(2):153-8
references.pmid: 15683685
references.citation: Am Rev Respir Dis. 1987 May;135(5):1165-76
references.pmid: 3555190
references.citation: Science. 1999 May 21;284(5418):1318-22
references.pmid: 10334980
references.citation: Clin Exp Pharmacol Physiol. 1995 Jun-Jul;22(6-7):387-96
references.pmid: 8582087
references.citation: Drugs Aging. 2009;26(5):363-79
references.pmid: 19552489
references.citation: Microbiology (Reading). 2007 Oct;153(Pt 10):3264-3274
references.pmid: 17906126
references.citation: Clin Allergy. 1982 Jan;12(1):19-27
references.pmid: 6175438
references.citation: N Engl J Med. 2008 Nov 27;359(22):2355-65
references.pmid: 19038881
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13899-904
references.pmid: 9811898
references.citation: Infect Immun. 2004 Jul;72(7):4275-8
references.pmid: 15213173