Title

Targeting junctional adhesion molecule-C ameliorates sepsis-induced acute lung injury by decreasing CXCR4+aged neutrophils

Publication Date

2018

Journal Title

J Leukoc Biol

Abstract

©2018 Society for Leukocyte Biology Sepsis is a severe inflammatory condition associated with high mortality. Transmigration of neutrophils into tissues increases their lifespan to promote deleterious function. Junctional adhesion molecule-C (JAM-C) plays a pivotal role in neutrophil transmigration into tissues. We aim to study the role of JAM-C on the aging of neutrophils to cause sepsis-induced acute lung injury (ALI). Sepsis was induced in C57BL/6J mice by cecal ligation and puncture (CLP) and JAM-C expression in serum was assessed. Bone marrow-derived neutrophils (BMDN) were treated with recombinant mouse JAM-C (rmJAM-C) ex vivo and their viability was assessed. CLP-operated animals were administrated with either isotype IgG or anti-JAM-C Ab at a concentration of 3 mg/kg and after 20 h, aged neutrophils (CXCR4+) were assessed in blood and lungs and correlated with systemic injury and inflammatory markers. Soluble JAM-C level in serum was up-regulated during sepsis. Treatment with rmJAM-C inhibited BMDN apoptosis, thereby increasing their lifespan. CLP increased the frequencies of CXCR4+neutrophils in blood and lungs, while treatment with anti-JAM-C Ab significantly reduced the frequencies of CXCR4+aged neutrophils. Treatment with anti-JAM-C Ab significantly reduced systemic injury markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) as well as systemic and lung inflammatory cytokines (IL-6 and IL-1β) and chemokine (macrophage inflammatory protein-2). The blockade of JAM-C improved lung histology and reduced neutrophil contents in lungs of septic mice. Thus, reduction of the pro-inflammatory aged neutrophils by blockade of JAM-C has a novel therapeutic potential in sepsis-induced ALI.

Volume Number

104

Issue Number

6

Pages

1159-1171

Document Type

Article

Status

Faculty; Northwell Researcher; Northwell Resident

Facility

School of Medicine; Northwell Health

Primary Department

Surgery

Additional Departments

Molecular Medicine

PMID

30088666

DOI

10.1002/JLB.3A0218-050R

For the public and Northwell Health campuses

Share

COinS