Neutrophil heterogeneity and emergence of a distinct population of CD11b/CD18-activated low-density neutrophils after trauma.
Journal
The journal of trauma and acute care surgery
ISSN: 2163-0763
Titre abrégé: J Trauma Acute Care Surg
Pays: United States
ID NLM: 101570622
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
pmc-release:
01
02
2024
entrez:
25
1
2023
pubmed:
26
1
2023
medline:
27
1
2023
Statut:
ppublish
Résumé
Multiple large clinical trauma trials have documented an increased susceptibility to infection after injury. Although neutrophils (polymorphonuclear leukocytes [PMNs]) were historically considered a homogeneous cell type, we hypothesized that injury could alter neutrophil heterogeneity and predispose to dysfunction. To explore whether trauma modifies PMN heterogeneity, we performed an observational mass-spectrometry-based cytometry study on total leukocytes and low-density PMNs found in the peripheral blood mononuclear cell fraction of leukocytes from healthy controls and trauma patients. A total of 74 samples from 12 trauma patients, each sampled at 1 or more time points, and matched controls were fractionated and profiled by mass-spectrometry-based cytometry using a panel of 44 distinct markers. After deconvolution and conservative gating on neutrophils, data were analyzed using Seurat, followed by clustering of principal components. Eleven distinct neutrophil populations were resolved in control and trauma neutrophils based on differential protein surface marker expression. Trauma markedly altered the basal heterogeneity of neutrophil subgroups seen in the control samples, with loss of a dominant population of resting neutrophils marked by high expression of C3AR and low levels of CD63, CD64, and CD177 (cluster 1), and expansion of two alternative neutrophil populations, one of which is marked by high expression of CD177 with suppression of CD10, CD16, C3AR, CD63, and CD64 (cluster 6). Remarkably, following trauma, a substantially larger percentage of neutrophils sediment in the monocyte fraction. These low-density neutrophils bear markers of functional exhaustion and form a unique trauma-induced population (cluster 9) with markedly upregulated expression of active surface adhesion molecules (activated CD11b/CD18), with suppression of nearly all other surface markers, including receptors for formyl peptides, leukotrienes, chemokines, and complement. Circulating neutrophils demonstrate considerable evidence of functional heterogeneity that is markedly altered by trauma. Trauma induces evolution of a novel, exhausted, low-density neutrophil population with immunosuppressive features.
Identifiants
pubmed: 36694330
doi: 10.1097/TA.0000000000003823
pii: 01586154-202302000-00002
pmc: PMC9881754
mid: NIHMS1844921
doi:
Substances chimiques
CD18 Antigens
0
Chemokines
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
187-196Subventions
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148232
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES028374
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES002109
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL120877
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI138318
Pays : United States
Informations de copyright
Copyright © 2022 American Association for the Surgery of Trauma.
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