Neutrophilic inflammation in the lung protects against infectious disease, and usually resolves spontaneously after removal of the inflammatory stimulus. However, much lung disease is caused by a failure of resolution of neutrophilic inflammation. Very little is known about how neutrophils are removed, so in order to better understand this process, a forward genetic mutagenesis screen was performed in zebrafish, looking for mutants with defective resolution of inflammation. In these mutants green fluorescent neutrophils persist at the site of inflammation.
We are currently performing detailed phenotyping as well as seeking the genetic basis of this mutant phenotype. Using these mutants we aim to identify key genes involved in neutrophil removal from sites of inflammation and ultimately identify compounds that target these genes that might be used to treat patients with respiratory disease.