Molecular mechanisms of neutrophil functions critical in lung injury

• Applicant: Professor Dr. Alexander Zarbock
• Subject Area: Anaesthesiology ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223566930

Neutrophil recruitment into the lung is of critical importance in the development of pulmonary inflammation and acute lung injury (ALI) caused by pneumonia, sepsis, aspiration of gastric content, and ventilator-induced lung injury. Under baseline conditions, neutrophils have a propensity to home to the lung through unknown mechanisms. Neutrophil recruitment is accelerated and enhanced during acid-induced ALI and bacterial lipopolysaccharide induced pulmonary inflammation. During the development of ALI many pro-inflammatory chemokines and cytokines are released by different cell types which modulate neutrophil recruitment and vascular permeability. The proposal consists of three aims in which we will investigate: 1) the molecular mechanisms by which platelet-neutrophil interactions result in TXA2 production and acute lung injury, 2) the importance of the three PAK isoforms for neutrophil recruitment into the lung, and 3) the molecular mechanisms by which 12/15 lipoxygenase exacerbates lung injury. This research is designed to identify points at which therapeutic interventions aimed at curbing neutrophil recruitment and lung injury may be feasible.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Jan Rossaint