1055 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model.

Wednesday, 14 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Taehyeong Lee , Soonchunhyang University, Asan, South Korea

Hyun Ji Song , Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea

Ji Ah Jun , Soonchunhyang University, Asan, South Korea

Jong-Sook Park, MD , Soonchunhyang University Bucheon Hospital, Bucheon, South Korea

Choon-Sik Park, MD., PhD. , Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea

Background: We previously reported elevation of S100 calcium binding protein A9 (S100A9) protein in sputum of neutrophilic uncontrolled asthmatics compared with stable asthmatics, [Annels of allergy, asthma, immunology on 2013 Oct;111(4):268-275], suggesting the possible role of S100A9 in neutrophilic severe asthma. The aim of this study was to validate the role of S100A9 expression in neutrophilic airway inflammation of OVA/CFA-sensitized/challenged murine asthma model.

Methods:Expression of S100A9 mRNA and protein was measured using a RT-PCR and western blot, respectively. Spatial expression of S100A9 protein and neutrophil elastase was visualized using immunofluorescene stain and confocal microscopy. To evaluate the potency of S100A9 on neutrophilic inflammation, temporal changes of neutrophil infiltration was analyzed in lung tissues of the OVA/CFA model and in those of C57BL/6 mice after intra-tracheal S100A9 protein (10ug) administration. To block the S100A9 in the airway, mice were treated with 20ul of anti-S100A9 antibody via intra-nasal route at 3 hour before challenge of S100A9.

Results: S100A9 started to increase from day 14 and peaked at day 23 while the number of total cells, macrophage and neutrophils significantly increased with a concomitant escalation of airway hyper-responsiveness (AHR) at day 23. Neutrophil elastase and S100A9 were co-localized in peri-bronchially infiltrating cells and in apical portion of bronchial epithelium. Intra-tracheal instillation of S100A9 induced a rapid increase of neutrophils in BAL fluid from 2 hr, which peaked at 24hr, and thereafter progressively decreased till 80 hr. Intra-nasal administration of anti-S100A9 antibody restored the increase of the numbers of inflammatory cells and AHR in CFA/OVA mice to those of sham mice.


Conclusion: S100A9 directly activates neutrophilic inflammation into the airway and neutrophils may be the major cell source of S100A9 protein, which suggests main role of the S100A9 protein in neutrophilic experimental asthma.