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Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.

Publication ,  Journal Article
Maskarinec, SA; McKelvy, M; Boyle, K; Hotchkiss, H; Duarte, ME; Addison, B; Amato, N; Khandelwal, S; Arepally, GM; Lee, GM
Published in: J Leukoc Biol
December 2022

Differences in the ability of neutrophils to perform relevant effector functions has been identified in a variety of disease states. Although neutrophil functional heterogeneity is increasingly recognized during disease, few studies have examined neutrophil functional heterogeneity during periods of health. In this study, we systematically characterize neutrophil functional heterogeneity in a cohort of healthy human subjects using a range of biologically relevant agonists including immune complexes, bacterial ligands, and pathogens. With repeated testing over several years, we show that neutrophil functional capability represents a fixed phenotype for each individual. This neutrophil phenotype is preserved across a range of agonists and extends to a variety of effector functions including degranulation, neutrophil extracellular trap release, reactive oxygen species generation, phagocytosis, and bacterial killing. Using well-phenotyped healthy human subjects, we demonstrate that neutrophil functional heterogeneity is characterized by differences in neutrophil gene expression patterns. Altogether, our findings demonstrate that while neutrophil function is highly heterogeneous among healthy subjects, each individual's functional capability represents a fixed phenotype defined by a distinct neutrophil gene expression profile. These findings may be relevant during disease states where the ability to perform relevant neutrophil effector functions may impact disease course and/or clinical outcome.

Duke Scholars

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Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

December 2022

Volume

112

Issue

6

Start / End Page

1485 / 1495

Location

England

Related Subject Headings

  • Transcriptome
  • Reactive Oxygen Species
  • Phenotype
  • Phagocytosis
  • Neutrophils
  • Immunology
  • Humans
  • Extracellular Traps
  • 3204 Immunology
  • 1107 Immunology
 

Citation

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Maskarinec, S. A., McKelvy, M., Boyle, K., Hotchkiss, H., Duarte, M. E., Addison, B., … Lee, G. M. (2022). Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles. J Leukoc Biol, 112(6), 1485–1495. https://doi.org/10.1002/JLB.4A0322-164R
Maskarinec, Stacey A., Margaret McKelvy, Kimberly Boyle, Halie Hotchkiss, Madelaine E. Duarte, Bechtler Addison, Nicholas Amato, Sanjay Khandelwal, Gowthami M. Arepally, and Grace M. Lee. “Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.J Leukoc Biol 112, no. 6 (December 2022): 1485–95. https://doi.org/10.1002/JLB.4A0322-164R.
Maskarinec SA, McKelvy M, Boyle K, Hotchkiss H, Duarte ME, Addison B, et al. Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles. J Leukoc Biol. 2022 Dec;112(6):1485–95.
Maskarinec, Stacey A., et al. “Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.J Leukoc Biol, vol. 112, no. 6, Dec. 2022, pp. 1485–95. Pubmed, doi:10.1002/JLB.4A0322-164R.
Maskarinec SA, McKelvy M, Boyle K, Hotchkiss H, Duarte ME, Addison B, Amato N, Khandelwal S, Arepally GM, Lee GM. Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles. J Leukoc Biol. 2022 Dec;112(6):1485–1495.

Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

December 2022

Volume

112

Issue

6

Start / End Page

1485 / 1495

Location

England

Related Subject Headings

  • Transcriptome
  • Reactive Oxygen Species
  • Phenotype
  • Phagocytosis
  • Neutrophils
  • Immunology
  • Humans
  • Extracellular Traps
  • 3204 Immunology
  • 1107 Immunology