Characterization of neutrophilic responses in a pollutant-aggravated asthma mouse model

Le résumé fourni par la source

Diesel exhaust particles (DEP) are implicated in the development and exacerbation of asthma. Combined exposure to DEP and house dust mite (HDM) in vivo induces an increase in eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF). However, it is unknown how neutrophils modulate the DEP-aggravated airway inflammation. C57BL/6J mice were intranasally exposed to saline, DEP, HDM or HDM+DEP. Neutrophils in BALF and lung tissue were quantified using flowcytometry and immunohistochemical staining, respectively. Several markers associated with neutrophil migration and activity were examined using ELISA and qPCR. Moreover, Human Bronchial Epithelial Cells (HBECs) were exposed to HDM or DEP alone or to the combination for 24 hours followed by measuring the expression of the neutrophil-attracting chemokines CXCL1 and CXCL8 using qPCR. Neutrophil numbers were significantly higher in BALF and in lung tissue of HDM+DEP-exposed mice compared to the control groups and were positively correlated with eosinophil numbers. The neutrophil-attracting chemokines CXCL1, CXCL2 and CXCL5 were significantly increased after HDM+DEP exposure. Double-stranded DNA and neutrophil elastase, components of neutrophil extracellular traps, were significantly elevated in the BALF of these mice. After combined HDM+DEP exposure, HBECs showed an increased mRNA expression of CXCL1 and CXCL8 compared to the controls. In conclusion, combined exposure to HDM+DEP induces neutrophilic responses both in a mouse model and in HBECs. These neutrophilic responses positively correlate with eosinophilic inflammation in vivo, which suggests an interaction between neutrophils and eosinophils in pollutant-aggravated allergic asthma.

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