Chemokines during anaphylaxis: the importance of CCL2 and CCL2-dependent chemotactic activity for basophils.
Anaphylaxis
Basophils
CCL2
Chemokines
Chemotaxis
Migration
Tryptase
Journal
Clinical and translational allergy
ISSN: 2045-7022
Titre abrégé: Clin Transl Allergy
Pays: England
ID NLM: 101576043
Informations de publication
Date de publication:
15 Dec 2020
15 Dec 2020
Historique:
received:
05
08
2020
accepted:
26
11
2020
entrez:
15
12
2020
pubmed:
16
12
2020
medline:
16
12
2020
Statut:
epublish
Résumé
The role of chemokines in anaphylaxis is unclear. We prospectively recruited 49 patients presenting to the emergency department with an acute episode of anaphylaxis and 28 healthy subjects. We measured serum levels of the chemokines CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL21, CCL22, CCL24, and CCL26, tryptase, the absolute number of circulating basophils, monocytes, lymphocytes, and PMNs, and whole blood FCER1A, CPA3 and HDC gene expression at two time points: during the anaphylactic episode and in convalescent samples collected approximately 3 months later. We then investigated the in vitro chemotactic activity of chemokines induced during anaphylaxis for the in vitro migration of the corresponding cells. Only CCL2 chemokine levels were significantly increased in anaphylaxis samples (median 514 pg/ml) compared to convalescent samples (284 pg/ml, P < 0.0001) and healthy subjects (279 pg/ml, P < 0.0001); there was no significant difference in any of the other chemokines. There was a significant positive correlation between the rates of increase of serum CCL2 (median [range]: 106.0% [- 44.7% to 557.4%]) and tryptase (133.8% [- 6.6% to 893.4%]; r = 0.68, P < 0.0001) and between the acute concentration of serum CCL2 and the acute concentration of serum tryptase (r = 0.77, P < 0.0001). The number of circulating basophils, but not other blood cells, significantly decreased during anaphylaxis (median 5.0 vs. 19.1 cells/µl in convalescent samples; P < 0.0001); a decrease in whole-blood gene expression of basophil markers (P ≤ 0.0018) confirmed these changes. Anaphylactic serum enhances the in vitro migration of basophils via CCL2-dependent chemotactic activity; in contrast, no CCL2-dependent chemotactic activity was observed for convalescent samples. Our findings imply an important and specific role for CCL2-mediated chemotactic activity in the pathophysiology of human anaphylaxis.
Sections du résumé
BACKGROUND
BACKGROUND
The role of chemokines in anaphylaxis is unclear.
METHODS
METHODS
We prospectively recruited 49 patients presenting to the emergency department with an acute episode of anaphylaxis and 28 healthy subjects. We measured serum levels of the chemokines CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL21, CCL22, CCL24, and CCL26, tryptase, the absolute number of circulating basophils, monocytes, lymphocytes, and PMNs, and whole blood FCER1A, CPA3 and HDC gene expression at two time points: during the anaphylactic episode and in convalescent samples collected approximately 3 months later. We then investigated the in vitro chemotactic activity of chemokines induced during anaphylaxis for the in vitro migration of the corresponding cells.
RESULTS
RESULTS
Only CCL2 chemokine levels were significantly increased in anaphylaxis samples (median 514 pg/ml) compared to convalescent samples (284 pg/ml, P < 0.0001) and healthy subjects (279 pg/ml, P < 0.0001); there was no significant difference in any of the other chemokines. There was a significant positive correlation between the rates of increase of serum CCL2 (median [range]: 106.0% [- 44.7% to 557.4%]) and tryptase (133.8% [- 6.6% to 893.4%]; r = 0.68, P < 0.0001) and between the acute concentration of serum CCL2 and the acute concentration of serum tryptase (r = 0.77, P < 0.0001). The number of circulating basophils, but not other blood cells, significantly decreased during anaphylaxis (median 5.0 vs. 19.1 cells/µl in convalescent samples; P < 0.0001); a decrease in whole-blood gene expression of basophil markers (P ≤ 0.0018) confirmed these changes. Anaphylactic serum enhances the in vitro migration of basophils via CCL2-dependent chemotactic activity; in contrast, no CCL2-dependent chemotactic activity was observed for convalescent samples.
CONCLUSIONS
CONCLUSIONS
Our findings imply an important and specific role for CCL2-mediated chemotactic activity in the pathophysiology of human anaphylaxis.
Identifiants
pubmed: 33317619
doi: 10.1186/s13601-020-00367-2
pii: 10.1186/s13601-020-00367-2
pmc: PMC7737350
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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