S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma

S100A9 as a biomarker for neutorphilic asthma A calcium-binding protein called S100A9 could be used as a biomarker for diagnosing a phenotype of asthma called neutrophilic asthma, and might also be a suitable target for drugs to treat the condition. Hae-Sim Park and colleagues at Ajou University in Suwon, South Korea, investigated the mechanism by which S100A9 activates neutrophils to induce the airway inflammation and other changes associated with asthma. Patients with neutrophilic asthma had higher levels of the protein in their blood. Measuring these levels could therefore be used as a potential biomarker. Serum biomarkers for identifying neutrophilic asthma are currently lacking. The research also supports the hypothesis that S100A9 plays a critical role in initiating and perpetuating the neutrophilic asthma and could become the therapeutic target. The biomarkers and therapeutic targets of neutrophilic asthma (NA) are poorly understood. Although S100 calcium-binding protein A9 (S100A9) has been shown to correlate with neutrophil activation, its role in asthma pathogenesis has not been clarified. This study investigated the mechanism by which S100A9 is involved in neutrophil activation, neutrophil extracellular trap (NET)-induced airway inflammation, and macrophage polarization in NA. The S100A9 levels (by ELISA) in sera/culture supernatant of peripheral blood neutrophils (PBNs) and M0 macrophages from asthmatic patients were measured and compared to those of healthy controls (HCs). The function of S100A9 was evaluated using airway epithelial cells (AECs) and PBNs/M0 macrophages from asthmatic patients, as well as a mouse asthma model. The serum levels of S100A9 were higher in NA patients than in non-NA patients, and there was a positive correlation between serum S100A9 levels and sputum neutrophil counts (r = 0.340, P = 0.005). Asthmatic patients with higher S100A9 levels had lower PC20 methacholine values and a higher prevalence of severe asthma (SA) (P < .050). PBNs/M0 macrophages from SA released more S100A9 than those from non-SA patients. PBNs from asthmatic patients induced S100A9 production by AECs, which further activated AECs via the extracellular signal-regulated kinase (ERK) pathway, stimulated NET formation, and induced M1 macrophage polarization. Higher S100A9 levels in sera, bronchoalveolar lavage fluid, and lung tissues were observed in the mouse model of NA but not in the other mouse models. These results suggest that S100A9 is a potential serum biomarker and therapeutic target for NA.

Automated summary

S100A9 is a potential serum biomarker and therapeutic target for neutrophilic asthma. Patients with neutrophilic asthma had higher levels of S100A9 protein in their blood, which could be used as a potential biomarker and therapeutic target.