Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics.
Airway inflammation
Allergic asthma
Coagulation
Mass spectrometry
Protease inhibition
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
05 Mar 2022
05 Mar 2022
Historique:
received:
03
09
2021
accepted:
14
02
2022
entrez:
6
3
2022
pubmed:
7
3
2022
medline:
18
3
2022
Statut:
epublish
Résumé
A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.
Sections du résumé
BACKGROUND
BACKGROUND
A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge.
METHODS
METHODS
Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models.
RESULTS
RESULTS
Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes.
CONCLUSIONS
CONCLUSIONS
Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.
Identifiants
pubmed: 35248034
doi: 10.1186/s12931-022-01968-0
pii: 10.1186/s12931-022-01968-0
pmc: PMC8897854
doi:
Substances chimiques
Allergens
0
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
50Subventions
Organisme : Vetenskapsrådet
ID : 2020-01375
Organisme : Hjärt-Lungfonden
ID : 20180171
Organisme : Hjärt-Lungfonden
ID : 20200651
Informations de copyright
© 2022. The Author(s).
Références
Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52
pubmed: 25352553
Nature. 2008 Dec 18;456(7224):989-92
pubmed: 19011614
Blood. 2010 Nov 25;116(22):4712-9
pubmed: 20716766
Stem Cells. 2002;20(6):585-7
pubmed: 12456967
Fibrogenesis Tissue Repair. 2013 Jan 17;6(1):2
pubmed: 23324174
Mol Cell Proteomics. 2020 Jun;19(6):1047-1057
pubmed: 32205417
J Allergy Clin Immunol. 2017 Sep;140(3):759-770.e13
pubmed: 27965111
J Clin Invest. 1979 Oct;64(4):1118-29
pubmed: 90057
Can Respir J. 2014 Sep-Oct;21(5):279-82
pubmed: 24791256
Am J Respir Crit Care Med. 2007 May 1;175(9):896-904
pubmed: 17272787
Mutat Res. 2010 Aug 7;690(1-2):24-39
pubmed: 19769993
J Allergy Clin Immunol. 1995 Dec;96(6 Pt 2):1076-82
pubmed: 8543765
J Lipid Res. 2015 Jun;56(6):1134-44
pubmed: 25896349
J Immunol. 2019 Jul 15;203(2):493-499
pubmed: 31160533
Clin Exp Allergy. 2017 Dec;47(12):1555-1565
pubmed: 28940836
J Immunol. 2015 Jan 1;194(1):142-50
pubmed: 25429068
ISRN Inflamm. 2013 Sep 14;2013:379040
pubmed: 24167754
J Pharm Bioallied Sci. 2011 Jan;3(1):118-27
pubmed: 21430962
Am J Respir Crit Care Med. 1999 Aug;160(2):640-7
pubmed: 10430741
Curr Mol Med. 2012 Jun;12(5):625-33
pubmed: 22292896
Respir Res. 2006 Mar 29;7:50
pubmed: 16571120
J Allergy Clin Immunol. 2013 Nov;132(5):1045-1055.e6
pubmed: 24119772
Immunobiology. 2006;211(6-8):609-18
pubmed: 16920499
Nat Med. 2012 May 04;18(5):716-25
pubmed: 22561835
Physiol Rev. 2011 Jul;91(3):931-72
pubmed: 21742792
Nat Biotechnol. 2010 Apr;28(4):337-40
pubmed: 20379180
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Nucleic Acids Res. 2021 Jan 8;49(D1):D325-D334
pubmed: 33290552
BMC Immunol. 2017 Jun 15;18(1):30
pubmed: 28619036
Nature. 1998 Jun 11;393(6685):595-9
pubmed: 9634238
J Immunol. 2003 Jul 1;171(1):380-9
pubmed: 12817021
J Lipid Res. 2014 Jun;55(6):1010-8
pubmed: 24548887
J Allergy Clin Immunol. 2016 Mar;137(3):767-73.e6
pubmed: 26525229
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Clin Exp Allergy. 2006 Apr;36(4):426-32
pubmed: 16630146
Trends Immunol. 2011 Oct;32(10):493-503
pubmed: 21802990
Eur Clin Respir J. 2016 Jul 13;3:31324
pubmed: 27421833
Top Companion Anim Med. 2012 May;27(2):46-52
pubmed: 23031455
J Thromb Haemost. 2017 Jul;15(7):1285-1294
pubmed: 28671350
Eur Clin Respir J. 2015 May 26;2:
pubmed: 26557261
Front Immunol. 2013 Dec 04;4:428
pubmed: 24363657
Am J Respir Crit Care Med. 2013 Oct 15;188(8):928-40
pubmed: 24050723
Front Immunol. 2018 Jun 11;9:1298
pubmed: 29942307
Clin Chim Acta. 2008 Feb;388(1-2):51-8
pubmed: 17963703
Sci Transl Med. 2009 Nov 4;1(5):5ra13
pubmed: 20368175
Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70-e88
pubmed: 31613151
Can Respir J. 2010 Jul-Aug;17(4):e85-93
pubmed: 20808979
Biomarkers. 2018 Feb;23(1):51-60
pubmed: 28862880
Front Immunol. 2018 Jul 30;9:1726
pubmed: 30105020