A unique population of neutrophils generated by air pollutant-induced lung damage exacerbates airway inflammation.

Abstract

BACKGROUND:

Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear.

OBJECTIVE:

This study aimed to identify a key cellular player of air pollutant-induced asthma exacerbation and development.

METHODS:

We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry and RNA-Seq analysis. The roles of sialic acid-binding, Ig-like lectin F (SiglecF)-positive neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies.

RESULTS:

DEP exposure induced a unique population of lung granulocytes that coexpressed Ly6G and SiglecF. These cells differed phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEPs induces the local release of adenosine triphosphate, which is a damage-associated molecular pattern signal. Adenosine triphosphate promotes the expression of SiglecF on neutrophils, and these SiglecF+ neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8- (which corresponds to murine SiglecF) expressing neutrophils, and we found it in patients with asthma-chronic obstructive pulmonary disease overlap.

CONCLUSION:

The SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting this population could reverse or ameliorate asthma.

• Authors: Jae Woo Shin, Jihyun Kim, Seokjin Ham, Sun Mi Choi, Chang-Hoon Lee, Jung Chan Lee, Ji Hyung Kim, Sang-Heon Cho, Hye Ryun Kang, You-Me Kim, Doo Hyun Chung, Yeonseok Chung, Yoe-Sik Bae, Yong-Soo Bae, Tae-Young Roh, Taesoo Kim, Hye Young Kim
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 149 Issue 4 Pg. 1253-1269.e8 (04 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 34653517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Air Pollutants
• Vehicle Emissions
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Air Pollutants (toxicity)
• Animals
• Asthma
• Humans
• Inflammation (metabolism)
• Lung
• Mice
• Neutrophils (pathology)
• Vehicle Emissions (toxicity)