Clever probes detect lung infection
Acute lung injury (ALI) is a clinical syndrome mainly encountered in patients hospitalised in the intensive care unit (ICU). ALI is characterised by heavy neutrophil infiltration in the lungs and often leads to ventilator-associated pneumonia (VAP), a cause of high mortality. Tracking ALI remains a major diagnostic challenge for critical care clinicians.Seeking to address this issue, the EU-funded ′New tools for real-time cellular imaging and protein labelling′ (CIPL) project proposed to develop specialised molecular imaging probes for detecting ALI and VAP. These activity-based probes were designed to either target neutrophils, the primary cause of ALI inflammation, or gram-negative and gram-positive bacteria.CIPL members tested a labelling moiety targeted against neutrophil enzymes such as caspase and human neutrophil elastase or bacterial equivalents. In vitro screening tests verified their discriminatory capacity against healthy lung tissue.Additionally CIPL researchers were interested in developing protein labelling methodology, which could be combined with their imaging probes. To this end, they utilised the well-established histidine tag as well as modified specific tyrosine residues on the protein. Detection of the modified proteins was performed by specific probes containing ligands against these tags and a fluorophore for imaging purposes.Although at their infancy, the CIPL optical molecular probes are expected to help identify critical inflammatory events in the lungs of ICU patients promptly. In the long-term, this method could be applied for rapidly and accurately determining the aetiology of deteriorating respiratory function or the clinical status of patients.
Keywords
Acute lung injury, imaging probes, inflammation, neutrophils, caspase, fluorophore, ligands
