Journal Article

Ozone-primed neutrophils promote early steps of tumour cell metastasis to lungs by enhancing their NET production

Gilles, Christine, Cataldo, Didier, Marichal, Thomas, Gillard, Alison, Radermecker, Coraline, Vanwinge, Céline, Evrard, Brigitte, Blacher, Silvia, Rocks, Natacha, Marée, Raphael, Noel, Agnes, Pequeux, Christel

2019

Overview

BackgroundAir pollution, including particulates and gazes such as ozone (O3), is detrimental for patient’s health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O3 exposure and metastatic dissemination to lungs.ObjectivesTo outline the mechanisms through which pulmonary O3 exposure modulates metastasis kinetics in an experimental mouse model of O3 exposure.MethodsMetastatic responses to pulmonary O3 exposure were assessed using a reliable experimental mouse model of concomitant pulmonary O3 exposure and tumour cell injection. Roles of neutrophils in O3-induced lung metastasis were highlighted using blocking anti-Ly6G antibodies; moreover, the implication of neutrophil extracellular traps (NETs) in metastatic processes was evaluated using MRP8cre-Pad4lox/lox mice or by treating mice with DNase I.ResultsPulmonary O3 exposure strongly facilitates the establishment of lung metastasis by (1) Inducing a pulmonary injury and neutrophilic inflammation, (2) Influencing very early steps of metastasis, (3) Priming neutrophils’ phenotype to release NETs that favour tumour cell colonisation in lungs. The ability of O3-primed neutrophils to enhance lung colonisation by tumour cells was proven after their adoptive transfer in Balb/c mice unexposed to O3.ConclusionsPulmonary neutrophils induced by O3 promote metastatic dissemination to lungs by producing NETs. These findings open new perspectives to improve treatment and prevention strategies in patients affected by metastatic diseases.

• Publisher: BMJ Publishing Group Ltd and British Thoracic Society,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Air pollution / Allergies / Animals / Antibodies - pharmacology / Antigens, Ly - immunology / Breast Neoplasms - pathology / Bronchitis - chemically induced / Bronchitis - pathology / Bronchoalveolar Lavage Fluid - cytology / Cancer therapies / Cell adhesion & migration / Cell Line, Tumor / Cells / Deoxyribonuclease I - pharmacology / Deoxyribonucleic acid / Disease Models, Animal / DNA / Extracellular Traps / Flow cytometry / General & internal medicine / Human health sciences / Immunology / Inflammation / Leukocyte Count / Lung cancer / Lung Injury - chemically induced / Lung Injury - pathology / Lung Neoplasms - pathology / Lung Neoplasms - secondary / Medical research / Melanoma / Melanoma - pathology / Metastasis / Mice / Mice, Inbred BALB C / Mortality / Médecine générale & interne / Neoplasm Metastasis - genetics / Neoplasm Transplantation / NET / Neutrophils / Neutrophils - drug effects / Neutrophils - pathology / Ozone / Ozone - toxicity / Ozone Pollution / Permeability / Pneumonia - chemically induced / Pneumonia - pathology / Pollutants / Protein-Arginine Deiminase Type 4 - genetics / Rodents / Sciences de la santé humaine