title: Neutrophil activation during acute human anaphylaxis: analysis of MPO and sCD62L.
abstract: BACKGROUND
  The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation.
  
  
  OBJECTIVE
  To investigate neutrophil activation in peripheral blood during acute human anaphylaxis.
  
  
  METHODS
  Patients presenting to the emergency department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time-points. Traditional anaphylaxis biomarkers, histamine and mast cell tryptase, were measured by ELISA and ImmunoCAP, respectively. Plasma myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L concentrations by cytometric bead array, and both compared to healthy controls.
  
  
  RESULTS
  In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine positive, and 47 (70%) were mast cell tryptase positive. At enrolment, myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4, 10.5) fold higher in moderate and severe patients, respectively, compared with healthy controls, and remained stable over the first 5 h following symptom onset. At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower in moderate and severe patients, respectively, than healthy controls, and was stable over the first 5 h. There were no associations between myeloperoxidase or soluble CD62L concentrations and either histamine or mast cell tryptase concentrations.
  
  
  CONCLUSIONS
  These results provide compelling evidence for the involvement of neutrophils during acute human anaphylaxis, suggesting they are activated early in the reaction, regardless of mast cell activation. This important finding increases our understanding of the basic mechanisms of anaphylaxis, a necessary precursor to improving treatment and prevention.
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-4356-7686
authors.initials: A
authors.lastname: Francis
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Bosio
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.
authors.forename: S F
authors.initials: SF
authors.lastname: Stone
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.|Emergency Department, Royal Perth Hospital, Perth, WA, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Fatovich
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.|Emergency Department, Royal Perth Hospital, Perth, WA, Australia.|Emergency Department, Fiona Stanley Hospital, Murdoch, WA, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Arendts
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Emergency Department, Fiona Stanley Hospital, Murdoch, WA, Australia.|Emergency Department, Fremantle Hospital, Fremantle, WA, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagree
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.|Emergency Department, Royal Perth Hospital, Perth, WA, Australia.|Emergency Department, Armadale Kelmscott Memorial Hospital, Mount Nasura, WA, Australia.
authors.forename: S P J
authors.initials: SP
authors.lastname: Macdonald
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Emergency Department, South West Health Campus, Bunbury, WA, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Mitenko
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Emergency Department, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Rajee
authors.affiliation: School of Medicine & Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Burrows
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.|Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Crawley, WA, Australia.|Emergency Department, Royal Perth Hospital, Perth, WA, Australia.|Emergency Department, Royal Hobart Hospital, Hobart, TAS, Australia.
authors.forename: S G A
authors.initials: SG
authors.lastname: Brown
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D006636:Histamine Release; D006801:Humans; D019041:L-Selectin / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D053802:Tryptases / Q000097:blood; D055815:Young Adult
chemical_list: D000485:Allergens; D015415:Biomarkers; D019041:L-Selectin; D009195:Peroxidase; D053802:Tryptases
keywords: anaphylaxis; basic mechanisms; clinical immunology; granulocyte; neutrophil; peripheral blood leucocyte