Nuclear segmentation facilitates neutrophil migration

Author:

Shen Connie12ORCID,Mulder Eva3,Buitenwerf Wiebe3,Postat Jérémy24,Jansen Aron56,Kox Matthijs56,Mandl Judith N.124ORCID,Vrisekoop Nienke3ORCID

Affiliation:

1. McGill University 1 Department of Microbiology and Immunology , , Montreal, H3A 2B4 , Canada

2. , McGill University 2 McGill Research Centre for Complex Traits , Montreal, H3G 0B1 , Canada

3. Department of Respiratory Medicine, Center of Translational Immunology, University Medical Center Utrecht 3 , 3584 EA, Utrecht , The Netherlands

4. McGill University 4 Department of Physiology , , Montreal, H3G 1Y6 , Canada

5. Radboud University Medical Center 5 Department of Intensive Care , , Nijmegen, 6525 GA , The Netherlands

6. , Radboud University Medical Center 6 Radboud Center for Infectious Diseases (RCI) , Nijmegen, 6525 GA , The Netherlands

Abstract

ABSTRACT Neutrophils are among the fastest-moving immune cells. Their speed is critical to their function as ‘first responder’ cells at sites of damage or infection, and it has been postulated that the unique segmented nucleus of neutrophils functions to assist their rapid migration. Here, we tested this hypothesis by imaging primary human neutrophils traversing narrow channels in custom-designed microfluidic devices. Individuals were given an intravenous low dose of endotoxin to elicit recruitment of neutrophils into the blood with a high diversity of nuclear phenotypes, ranging from hypo- to hyper-segmented. Both by cell sorting of neutrophils from the blood using markers that correlate with lobularity and by directly quantifying the migration of neutrophils with distinct lobe numbers, we found that neutrophils with one or two nuclear lobes were significantly slower to traverse narrower channels, compared to neutrophils with more than two nuclear lobes. Thus, our data show that nuclear segmentation in primary human neutrophils provides a speed advantage during migration through confined spaces.

Funder

Canadian Institutes of Health Research

Fonds de Recherche du Québec – Santé

McGill University

Publisher

The Company of Biologists

Subject

Cell Biology

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