GEF-H1 is necessary for neutrophil shear stress–induced migration during inflammation-Reference-Cited by-同舟云学术

GEF-H1 is necessary for neutrophil shear stress–induced migration during inflammation

Published:2016-10-10 Issue:1 Volume:215 Page:107-119
ISSN:0021-9525
Container-title:Journal of Cell Biology
language:en
Short-container-title:

Author:

Fine Noah¹²³^ORCID,Dimitriou Ioannis D.¹⁴^ORCID,Rullo Jacob⁵,Sandí María José¹^ORCID,Petri Björn⁶^ORCID,Haitsma Jack⁷^ORCID,Ibrahim Hisham⁵,La Rose Jose¹,Glogauer Michael³^ORCID,Kubes Paul⁶,Cybulsky Myron⁵^ORCID,Rottapel Robert¹²⁴⁸⁵

Affiliation:

1. Princess Margaret Cancer Center, Toronto, Ontario M5G 1L7, Canada

2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 1L7, Canada

3. Matrix Dynamics Group, University of Toronto, Toronto, Ontario M5S 3E2, Canada

4. Department of Immunology, University of Toronto, Toronto, Ontario M5S 1L7, Canada

5. Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada

6. Immunology Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Infection, Immunity and Inflammation, University of Calgary, Calgary, Alberta T2N 4N1, Canada

7. Department of Anesthesiology, VU Medical Center, 1081 HV Amsterdam, Netherlands

8. Department of Medicine, University of Toronto, Toronto, Ontario M5S 1L7, Canada

Abstract

Leukocyte crawling and transendothelial migration (TEM) are potentiated by shear stress caused by blood flow. The mechanism that couples shear stress to migration has not been fully elucidated. We found that mice lacking GEF-H1 (GEF-H1−/−), a RhoA-specific guanine nucleotide exchange factor (GEF), displayed limited migration and recruitment of neutrophils into inflamed tissues. GEF-H1−/− leukocytes were deficient in in vivo crawling and TEM in the postcapillary venules. We demonstrated that although GEF-H1 deficiency had little impact on the migratory properties of neutrophils under static conditions, shear stress triggered GEF-H1–dependent spreading and crawling of neutrophils and relocalization of GEF-H1 to flotillin-2–rich uropods. Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.

Funder

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Publisher

Rockefeller University Press

Subject

Cell Biology

Link

http://rupress.org/jcb/article-pdf/215/1/107/1065920/jcb_201603109.pdf

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