Williams, Carmen (NIEHS)
Lin, Wan-Chi (NIEHS)
During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.
NIEHS researchers identified epithelial membrane protein 2 (EMP2) as a lung epithelial protein that regulates PMN entry into the inflamed airspace. EMP2 knockout mice have reduced PMN accumulation and exhibit increased survival during bacterial infection.
An EMP2 inhibitor can be developed for the treatment or prophylaxis for a wide variety of neutrophil-dependent lung disorders, such as:.
- acute lung injury
- pneumonia (bacterial, viral, fungal)
- COPD and asthma
- radiation- or chemotherapeutic-induced pneumonitis
- idiopathic or induced interstitial lung disease
- bronchopulmonary dysplasia
- lung transplant rejection
- EMP2 can selectively target PMN accumulation in the lung, rather than broadly affecting PMN trafficking through all tissues