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Szymczak K, Pelletier MGH, Malu K, et al. Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils. Immunohorizons. 2022;6(1):16-35doi: 10.4049/immunohorizons.2100072.
Szymczak, K., Pelletier, M. G. H., Malu, K., Barbeau, A. M., Giadone, R. M., Babroudi, S. C., & Gaines, P. C. W. (2022). Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils. ImmunoHorizons, 6(1), 16-35. https://doi.org/10.4049/immunohorizons.2100072
Szymczak, Klaudia, et al. "Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils." ImmunoHorizons vol. 6,1 (2022): 16-35. doi: https://doi.org/10.4049/immunohorizons.2100072
Szymczak K, Pelletier MGH, Malu K, Barbeau AM, Giadone RM, Babroudi SC, Gaines PCW. Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils. Immunohorizons. 2022 Jan 17;6(1):16-35. doi: 10.4049/immunohorizons.2100072. PMID: 35039433.
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Immunohorizons. 2022 Jan 17;6(1):16-35. doi: 10.4049/immunohorizons.2100072.

Expression Levels of Lamin A or C Are Critical to Nuclear Maturation, Functional Responses, and Gene Expression Profiles in Differentiating Mouse Neutrophils.

ImmunoHorizons

Klaudia Szymczak, Margery G H Pelletier, Krishnakumar Malu, Anna M Barbeau, Richard M Giadone, Seda C Babroudi, Peter C W Gaines

Affiliations

  1. Department of Biological Sciences, Biomedical Engineering and Biotechnology Program, University of Massachusetts Lowell, Lowell, MA.
  2. Department of Biological Sciences, Biomedical Engineering and Biotechnology Program, University of Massachusetts Lowell, Lowell, MA [email protected].

PMID: 35039433 DOI: 10.4049/immunohorizons.2100072

Abstract

Neutrophils mediate critical innate immune responses by migrating to sites of infection or inflammation, phagocytosing microorganisms, and releasing an arsenal of antimicrobial agents, including reactive oxygen species. These functions are shared by other innate immune cell types, but an interesting feature of neutrophils is their hallmark lobulated nuclei. Although why this bizarre nuclear shape forms is still being elucidated, studies of two intermediate filament proteins that associate with the nuclear envelope, lamin A and C, indicate that expression levels of these proteins govern nuclear maturation. These A-type lamins also modulate nuclear stiffness, the loss of which may be critical to the migration of not only neutrophils but also cancer cells that become prone to metastasis. We investigated whether increased expression of either lamin A or C affects neutrophil nuclear morphologic maturation, but more importantly we tested whether overexpression of either lamin also affects neutrophil functional responses, using two mouse myeloid progenitor models that can be induced toward functionally responsive neutrophil-like cells. Collectively, our results demonstrate that overexpression of either lamin A or C not only disrupts nuclear lobulation but also causes aberrant functional responses critical to innate immunity, including chemotaxis, phagocytosis, and reactive oxygen species production. Moreover, the lamin A-overexpressing cells exhibit decreased expression of a critical NADPH oxidase complex factor, gp91

Copyright © 2022 The Authors.

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