Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Gα13 Mediates Transendothelial Migration of Neutrophils by Promoting Integrin-Dependent Motility without Affecting Directionality

Claire W. Chang, Ni Cheng, Yanyan Bai, Randal A. Skidgel and Xiaoping Du
J Immunol December 15, 2021, 207 (12) 3038-3049; DOI: https://doi.org/10.4049/jimmunol.2001385
Claire W. Chang
*Department of Pharmacology, University of Illinois at Chicago, Chicago, IL;
†Department of Bioengineering, University of Illinois at Chicago, Chicago, IL; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Claire W. Chang
Ni Cheng
*Department of Pharmacology, University of Illinois at Chicago, Chicago, IL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ni Cheng
Yanyan Bai
*Department of Pharmacology, University of Illinois at Chicago, Chicago, IL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Randal A. Skidgel
‡Dupage Medical Technology, Inc., Chicago, IL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoping Du
*Department of Pharmacology, University of Illinois at Chicago, Chicago, IL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • Gα13 plays a role in integrin-dependent neutrophil transendothelial migration.

  • Gα13 enhances motility but did not affect directionality of neutrophil migration.

  • Integrin outside-in signaling mediates Gα13-dependent neutrophil migration.

Abstract

Neutrophil migration requires β2 integrins and chemoattractant receptor signaling for motility and directionality. G protein subunit Gα13 can facilitate cell migration by mediating RhoA activation induced by G protein–coupled receptors. However, the possible role of Gα13-integrin interaction in migration is unclear. In this study, we show that Gα13−/− neutrophils are deficient in transendothelial migration and migration on β2 integrin ligand ICAM-1. However, unlike G protein–coupled receptors and integrin inside-out signaling pathways, Gα13 is important in migration velocity and neutrophil spreading but not in directionality nor cell adhesion. Importantly, neutrophil recruitment in vivo was also inhibited in Gα13−/− mice, suggesting the importance of Gα13 in transendothelial migration of neutrophils in vitro and in vivo. Furthermore, a synthetic peptide (MB2mP6) derived from the Gα13 binding site of β2 inhibited Gα13-β2 interaction and Gα13-mediated transient RhoA inhibition in neutrophils, suggesting that this peptide inhibited integrin outside-in signaling. MB2mP6 inhibited migration of control neutrophils through endothelial cell monolayers or ICAM-1–coated filters, but was without further effect on Gα13−/− neutrophils. It also inhibited integrin-dependent neutrophil migration velocity without affecting directionality. In vivo, MB2mP6 markedly inhibited neutrophil infiltration into the cardiac tissues induced by ischemia/reperfusion injury. Thus, Gα13-dependent outside-in signaling enables integrin-dependent neutrophil motility without affecting directionality and may be a new therapeutic target for inhibiting neutrophil trafficking but not adhesion.

This article is featured in Top Reads, p.

Footnotes

  • This work was supported by National Heart, Lung and Blood Institute Grants R35HL150797 (X.D.), RO1HL125356 (X.D.), RO1HL080264 (X.D.), R43 HL142396 (R.A.S.), and R44 HL142396 (R.A.S.).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article

    fMIVIL
    N-formyl-Met-Ile-Val-Ile-Leu
    GEF
    guanine nucleotide exchange factor
    GPCR
    G protein-coupled receptor
    HLPN
    high-loading peptide nanoparticle
    MI/R
    myocardial ischemia/reperfusion

  • Received January 8, 2021.
  • Accepted October 7, 2021.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
View Full Text

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Log in using your username and password

Forgot your user name or password?
PreviousNext
Back to top

In this issue

The Journal of Immunology: 207 (12)
The Journal of Immunology
Vol. 207, Issue 12
15 Dec 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Advertising (PDF)
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Gα13 Mediates Transendothelial Migration of Neutrophils by Promoting Integrin-Dependent Motility without Affecting Directionality
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Gα13 Mediates Transendothelial Migration of Neutrophils by Promoting Integrin-Dependent Motility without Affecting Directionality
Claire W. Chang, Ni Cheng, Yanyan Bai, Randal A. Skidgel, Xiaoping Du
The Journal of Immunology December 15, 2021, 207 (12) 3038-3049; DOI: 10.4049/jimmunol.2001385

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Gα13 Mediates Transendothelial Migration of Neutrophils by Promoting Integrin-Dependent Motility without Affecting Directionality
Claire W. Chang, Ni Cheng, Yanyan Bai, Randal A. Skidgel, Xiaoping Du
The Journal of Immunology December 15, 2021, 207 (12) 3038-3049; DOI: 10.4049/jimmunol.2001385
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mouse Trophoblast Cells Can Provide IFN-Based Antiviral Protection to Embryonic Stem Cells via Paracrine Signaling
  • Thrombin Differentially Modulates the Acute Inflammatory Response to Escherichia coli and Staphylococcus aureus in Human Whole Blood
  • The Intracellular Interaction of Porcine β-Defensin 2 with VASH1 Alleviates Inflammation via Akt Signaling Pathway
Show more INNATE IMMUNITY AND INFLAMMATION

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606