title: Mediators released during human anaphylaxis.
abstract: A range of mediators are generated during anaphylaxis, with redundancy of effects, multiple overlapping pathways, and involvement of several cell types. Key steps in the reaction occur at the site of initial contact, and mediators may not be detectable systemically. Furthermore, the potencies of various mediators vary enormously, and clinical effects may occur below our level of detection. We also do not know what converts (amplifies) a local reaction into systemic anaphylaxis. Murine models have identified several novel mediators that may propagate and/or regulate this process and also indicate that circulating neutrophils may play an important role in reaction amplification. Differential expression of various genes within specific intracellular signalling pathways of mediator release may further explain the varying severities of anaphylactic reactions. As our knowledge of the mechanisms of activation, key mediators, and the regulation of mediator release improves, new treatments for prevention and acute management may emerge.
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Western Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia, Australia. Shelley.Stone@uwa.edu.au
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Stone
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
mesh_terms: D000707:Anaphylaxis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D004342:Drug Hypersensitivity / Q000150:complications; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D007073:Immunoglobulin E
references.citation: J Biol Chem. 2011 Mar 18;286(11):9503-13
references.pmid: 21212279
references.citation: J Allergy Clin Immunol. 2011 Aug;128(2):424-6.e1
references.pmid: 21555149
references.citation: Curr Opin Allergy Clin Immunol. 2007 Aug;7(4):331-6
references.pmid: 17620825
references.citation: Ann Allergy Asthma Immunol. 2010 Nov;105(5):364-8
references.pmid: 21055662
references.citation: J Immunol. 2011 Jul 15;187(2):932-41
references.pmid: 21653832
references.citation: Forensic Sci Int. 2011 Oct 10;212(1-3):96-101
references.pmid: 21664082
references.citation: J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):150-8
references.pmid: 10887318
references.citation: Ann Allergy Asthma Immunol. 2000 Nov;85(5):368-71
references.pmid: 11101177
references.citation: PLoS One. 2010 Oct 28;5(10):e13707
references.pmid: 21060839
references.citation: J Allergy Clin Immunol. 2001 Jan;107(1):191-3
references.pmid: 11150011
references.citation: Ann Allergy Asthma Immunol. 2006 Mar;96(3):415-21
references.pmid: 16597075
references.citation: Immunol Lett. 2000 Nov 1;74(3):233-7
references.pmid: 11064108
references.citation: Allergy. 2011 Jan;66(1):1-14
references.pmid: 20560905
references.citation: J Immunol. 2007 Nov 15;179(10):6696-703
references.pmid: 17982059
references.citation: Toxicol Appl Pharmacol. 2011 Jul 1;254(1):56-64
references.pmid: 21515303
references.citation: Chem Immunol Allergy. 2010;95:45-66
references.pmid: 20519881
references.citation: J Allergy Clin Immunol. 2009 Oct;124(4):786-92.e4
references.pmid: 19767073
references.citation: Clin Transl Sci. 2010 Aug;3(4):158-69
references.pmid: 20718816
references.citation: J Allergy Clin Immunol. 2007 Apr;119(4):780-91
references.pmid: 17321578
references.citation: Curr Opin Allergy Clin Immunol. 2003 Aug;3(4):287-93
references.pmid: 12865773
references.citation: J Immunol. 2010 Nov 15;185(10):5993-6002
references.pmid: 20944008
references.citation: Allergy. 2007 Jul;62(7):717-22
references.pmid: 17573717
references.citation: J Allergy Clin Immunol. 2011 Jun;127(6):1552-61.e1
references.pmid: 21624619
references.citation: Adv Exp Med Biol. 2011;716:212-34
references.pmid: 21713659
references.citation: J Immunol. 1997 Aug 15;159(4):1987-92
references.pmid: 9257865
references.citation: J Allergy Clin Immunol. 2011 Dec;128(6):1259-1265.e2
references.pmid: 21794906
references.citation: J Innate Immun. 2011;3(5):459-70
references.pmid: 21502744
references.citation: J Allergy Clin Immunol. 2009 Feb;123(2):434-42
references.pmid: 19117599
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12413-8
references.pmid: 21746933
references.citation: Chem Immunol Allergy. 2010;95:98-109
references.pmid: 20519884
references.citation: Prostaglandins Leukot Med. 1986 Mar;21(3):269-77
references.pmid: 3010331
references.citation: Immunol Invest. 2010;39(7):740-53
references.pmid: 20840058
references.citation: Adv Exp Med Biol. 2011;716:123-42
references.pmid: 21713655
references.citation: Ann Allergy Asthma Immunol. 2009 May;102(5):403-9
references.pmid: 19492662
references.citation: J Allergy Clin Immunol. 2009 Oct;124(4):639-46; quiz 647-8
references.pmid: 19815110
references.citation: Nat Immunol. 2010 Jul;11(7):601-7
references.pmid: 20526344
references.citation: J Immunol. 2003 Mar 15;170(6):3306-14
references.pmid: 12626590
references.citation: Clin Exp Allergy. 2003 Aug;33(8):1033-40
references.pmid: 12911775
references.citation: J Forensic Sci. 2011 Mar;56(2):526-8
references.pmid: 21265844
references.citation: Nat Med. 2010 Oct;16(10):1128-33
references.pmid: 20835248
references.citation: Med J Aust. 2007 Jun 18;186(12):618-21
references.pmid: 17576175
references.citation: Med Clin North Am. 2010 Jul;94(4):645-64, xv
references.pmid: 20609855
references.citation: J Biol Chem. 2009 Nov 20;284(47):32344-52
references.pmid: 19776007
references.citation: J Allergy Clin Immunol. 2007 Apr;119(4):1016-8
references.pmid: 17306354
references.citation: Inflammation. 2011 Oct;34(5):314-8
references.pmid: 20706780
references.citation: J Allergy Clin Immunol. 2010 Dec;126(6):1208-17.e3
references.pmid: 21134573
references.citation: Eur Respir J. 1993 Nov;6(10):1468-73
references.pmid: 8112440
references.citation: J Allergy Clin Immunol. 2006 Jun;117(6):1440-5
references.pmid: 16751011
references.citation: J Allergy Clin Immunol. 2009 Mar;123(3):689-93
references.pmid: 19217654
references.citation: N Engl J Med. 2008 Jan 3;358(1):28-35
references.pmid: 18172172
references.citation: J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):65-71
references.pmid: 10887307
references.citation: J Pharmacol Sci. 2011;115(4):500-8
references.pmid: 21498955
references.citation: Emerg Med Australas. 2004 Apr;16(2):120-4
references.pmid: 15239726
references.citation: PLoS One. 2010 Aug 03;5(8):e11944
references.pmid: 20689814
references.citation: Am J Physiol Cell Physiol. 2010 Nov;299(5):C1007-14
references.pmid: 20686074
references.citation: Nature. 2004 Oct 21;431(7011):1007-11
references.pmid: 15496927
references.citation: Ann Emerg Med. 2006 Apr;47(4):373-80
references.pmid: 16546624
references.citation: J Allergy Clin Immunol. 2007 Oct;120(4):878-84
references.pmid: 17931562
references.citation: J Allergy Clin Immunol. 1993 Feb;91(2):605-15
references.pmid: 7679683
references.citation: J Allergy Clin Immunol. 2009 Feb;123(2):342-51
references.pmid: 19121857
references.citation: J Allergy Clin Immunol. 2010 Aug;126(2):385-8
references.pmid: 20621344
references.citation: Chem Immunol Allergy. 2010;95:85-97
references.pmid: 20519883
references.citation: J Allergy Clin Immunol. 2007 Sep;120(3):506-15; quiz 516-7
references.pmid: 17765751
references.citation: J Clin Invest. 2011 Apr;121(4):1484-96
references.pmid: 21436586
references.citation: J Immunol. 2011 Aug 15;187(4):1807-15
references.pmid: 21746961
references.citation: J Allergy Clin Immunol. 2006 Feb;117(2):391-7
references.pmid: 16461139
references.citation: Ann Allergy Asthma Immunol. 2009 Dec;103(6):488-95
references.pmid: 20084842
references.citation: Curr Opin Allergy Clin Immunol. 2008 Aug;8(4):310-5
references.pmid: 18596587
references.citation: J Exp Med. 2010 Mar 15;207(3):465-74
references.pmid: 20194630
references.citation: Curr Opin Allergy Clin Immunol. 2007 Jun;7(3):279-87
references.pmid: 17489049
references.citation: J Allergy Clin Immunol. 2010 May;125(5):1137-1145.e6
references.pmid: 20392487
references.citation: Med Humanit. 2005 Jun;31(1):12-6
references.pmid: 16167409
references.citation: J Allergy Clin Immunol. 2000 May;105(5):847-59
references.pmid: 10808163
references.citation: Am J Emerg Med. 2005 Oct;23(6):763-6
references.pmid: 16182985
references.citation: J Investig Allergol Clin Immunol. 2007;17(6):379-85
references.pmid: 18088020
references.citation: Nat Rev Immunol. 2009 Jan;9(1):9-13
references.pmid: 19039320
references.citation: Allergy. 2011 Jul;66 Suppl 95:31-4
references.pmid: 21668849
references.citation: Immunol Allergy Clin North Am. 2007 May;27(2):165-75, v
references.pmid: 17493496