期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 12, 页码 8610-8618出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.441535
关键词
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资金
- Cross-Disciplinary Fellowship of the International Human Frontiers Science Program (HFSP)
- National Institutes of Health [R01 NS059348, R01 HL082792, CA-16042, AI-28697]
- Department of Defense [BC102152]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- American Heart Association (AHA) [09POST2320042]
- HFSP [RGP0004/2005-C102]
- National Science Foundation (NSF) [DMR-1006546, DBI-649865]
- Harvard Materials Research Science and Engineering Center (MRSEC) [DMR-0820484]
- JCCC
- UCLA AIDS Institute
- David Geffen School of Medicine at UCLA
- UCLA Chancellor's Office
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1006546] Funding Source: National Science Foundation
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-Huet 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.
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