Evidence map›Paper›PMID 26858400›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts.

Meredith E Fay, David R Myers, Amit Kumar, Cory T Turbyfield, Rebecca Byler, Kaci Crawford, Robert G Mannino, Alvin Laohapant, Erika A Tyburski, Yumiko Sakurai and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.

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  16. Distinctive features and prognostic utility of neutrophil in severe patients withFrontiers in cellular and infection microbiology · 2024
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Meredith E FayThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
David R MyersThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Amit KumarDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706;
Cory T TurbyfieldThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
Rebecca BylerThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
Kaci CrawfordThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
Robert G ManninoThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Alvin LaohapantThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Erika A TyburskiThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Yumiko SakuraiThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Michael J RosenbluthThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332;
Neil A SwitzPhysics Faculty, The Evergreen State College, Olympia, WA 98505.
Todd A SulchekGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
Michael D GrahamDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706;ORCID http://orcid.org/0000-0003-4983-4949
Wilbur A LamThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322; Winship Cancer Institute, Emory University, Atlanta, GA 30322; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA 30332; wilbur.lam@emory.edu.
Georgia Institute of Technology · USUniversity of Wisconsin–Madison · USThe Evergreen State College · US

Funding

Endothelialized microfluidics for sickle cell disease research & drug discoveryR01HL121264 · NHLBI · EMORY UNIVERSITY · PI LAM, WILBUR A · 2014 to 2018
$2.0M
NHLBI NIH HHS R01 HL121264
6 · The paper itself

Abstract

Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones, although the underlying mechanisms remain unclear. Here we show that alterations in granulocyte mechanical properties are the driving force behind glucocorticoid- and catecholamine-induced demargination. First, we found that the proportions of granulocytes from healthy human subjects that traversed and demarginated from microfluidic models of capillary beds and veins, respectively, increased after the subjects ingested glucocorticoids. Also, we show that glucocorticoid and catecholamine exposure reorganizes cellular cortical actin, significantly reducing granulocyte stiffness, as measured with atomic force microscopy. Furthermore, using simple kinetic theory computational modeling, we found that this reduction in stiffness alone is sufficient to cause granulocyte demargination. Taken together, our findings reveal a biomechanical answer to an old hematologic question regarding how glucocorticoids and catecholamines cause leukocyte demargination. In addition, in a broader sense, we have discovered a temporally and energetically efficient mechanism in which the innate immune system can simply alter leukocyte stiffness to fine tune margination/demargination and therefore leukocyte trafficking in general. These observations have broad clinically relevant implications for the inflammatory process overall as well as hematopoietic stem cell mobilization and homing.

Indexed as

Cell MovementGranulocytesLab-On-A-Chip DevicesModels, CardiovascularCatecholaminesFemaleGlucocorticoidsHumansLeukocyte CountMaleCatecholaminesGlucocorticoidsatomic force microscopycellular mechanicsdemarginationleukocyte deformabilitymicrofluidics

Identifiers

PMID26858400
PMCPMC4776450
OpenAlexW2275060683

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.