Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions

Authors

Amy C. Rowat
Diana E. Jaalouk E. Jaalouk
Monika Zwerger
W. Lloyd Ung
Irwin A. Eydelnant
Donald E. Olins, University of New EnglandFollow
Ada L. Olins, University of New EnglandFollow
Harald Herrmann
David A. Weitz
Jan Lammerding

Document Type

Article

Publication Date

1-25-2013

Abstract

Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huët anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed shape of the neutrophil nucleus is less essential.

Comments

This research was originally published in the Journal of Biological Chemistry. Rowat AC, Jaalouk DE, Zwerger M, et al. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J Biol Chem. 2013;288(12):8610–8618. doi:10.1074/jbc.M112.441535
© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Supplementary materials retrieved from: http://www.jbc.org/content/288/12/8610/suppl/DC1

Recommended Citation

Rowat, Amy C.; Jaalouk, Diana E. Jaalouk E.; Zwerger, Monika; Ung, W. Lloyd; Eydelnant, Irwin A.; Olins, Donald E.; Olins, Ada L.; Herrmann, Harald; Weitz, David A.; and Lammerding, Jan, "Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions" (2013). Pharmaceutical Sciences Faculty Publications. 22.
https://dune.une.edu/pharmsci_facpubs/22