CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation

Bai M, Grieshaber-Bouyer R, Wang J, Schmider AB, Wilson ZS, Zeng L, Halyabar O, Godin MD, Nguyen HN, Levescot A, Cunin P, Lefort CT, Soberman RJ, Nigrovic PA (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Blood American Society of Hematology

Book Volume: 130

Pages Range: 2092-2100

Journal Issue: 19

DOI: 10.1182/blood-2017-03-768507

Abstract

CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with b2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177^pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177^pos and CD177^neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177^pos neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with b2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface b2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a b2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration.

Authors with CRIS profile

Ricardo Grieshaber Bouyer

Involved external institutions

Brigham and Women's Hospital (BWH)

United States (USA) (US) Massachusetts General Hospital

United States (USA) (US) Rhode Island Hospital

United States (USA) (US) Novartis Institutes for BioMedical Research, Inc.

United States (USA) (US)

How to cite

APA:

Bai, M., Grieshaber-Bouyer, R., Wang, J., Schmider, A.B., Wilson, Z.S., Zeng, L.,... Nigrovic, P.A. (2017). CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation. Blood, 130(19), 2092-2100. https://doi.org/10.1182/blood-2017-03-768507

MLA:

Bai, Ming, et al. "CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation." Blood 130.19 (2017): 2092-2100.

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