Journal article
TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production
Journal of leukocyte biology, Vol.105(6), pp.1195-1207
06/2019
DOI: 10.1002/JLB.3VMA0918-375R
PMCID: PMC6708376
PMID: 30667543
Abstract
Neutrophil migration across tissue barriers to the site of injury involves integration of complex danger signals and is critical for host survival. Numerous studies demonstrate that these environmental signals fundamentally alter the responses of extravasated or "primed" neutrophils. Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a central role in modulating inflammatory signaling and neutrophil migration into the alveolar airspace. Using a genetic approach, we examined the role of TREM-1 in extravasated neutrophil function. Neutrophil migration in response to chemoattractants is dependent upon multiple factors, including reactive oxygen species (ROS) generated either extracellularly by epithelial cells or intracellularly by NADPH oxidase (NOX). We, therefore, questioned whether ROS were responsible for TREM-1-mediated regulation of migration. Thioglycollate-elicited peritoneal neutrophils isolated from wild-type (WT) and TREM-1-deficient mice were stimulated with soluble and particulate agonists. Using electron paramagnetic resonance spectroscopy, we demonstrated that NOX2-dependent superoxide production is impaired in TREM-1-deficient neutrophils. Consistent with these findings, we confirmed with Clark electrode that TREM-1-deficient neutrophils consume less oxygen. Next, we demonstrated that TREM-1 deficient neutrophils have impaired directional migration to fMLP and zymosan-activated serum as compared to WT neutrophils and that deletion or inhibition of NOX2 in WT but not TREM-1-deficient neutrophils significantly impaired direction sensing. Finally, TREM-1 deficiency resulted in decreased protein kinase B (AKT) activation. Thus, TREM-1 regulates neutrophil migratory properties, in part, by promoting AKT activation and NOX2-dependent superoxide production. These findings provide the first mechanistic evidence as to how TREM-1 regulates neutrophil migration.
Details
- Title: Subtitle
- TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production
- Creators
- Sankar Baruah - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAShubha Murthy - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAKathy Keck - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAIsabel Galvan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAAllan Prichard - Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, USALee-Ann H Allen - Iowa City VA Healthcare System, Iowa City, Iowa, USAMary Farrelly - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAJulia Klesney-Tait - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.105(6), pp.1195-1207
- DOI
- 10.1002/JLB.3VMA0918-375R
- PMID
- 30667543
- PMCID
- PMC6708376
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Grant note
- P30 ES005605 / NIEHS NIH HHS UL1 TR002537 / NCATS NIH HHS I01 BX002108 / BLRD VA P30 DK054759 / NIDDK NIH HHS P30 CA086862 / NCI NIH HHS R01 AI119965 / NIAID NIH HHS R01 HL121105 / NHLBI NIH HHS
- Language
- English
- Date published
- 06/2019
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094313202771
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