Studying inflammation in the zebrafish
Neutrophils constitute the first line of defence of our innate immune system. However, our understanding of the inflammatory mechanisms and the complex cell–cell communications that regulate resolution of inflammation is limited. Many studies on inflammation have benefited from using the zebrafish model as a research tool. The optical transparency of the animal and its genetic accessibility make it ideal for studying many biological processes. Transgenic fish expressing fluorescent proteins in white blood cells allow direct quantification of the inflammatory response in real time. Scientists on the EU-funded 'Regulation of inflammation' (INFLAM) project developed a novel wounding assay in zebrafish to delineate the events that lead to inflammation. This assay is based on chemical wounding using a plethora of compounds, followed by microscopic visualisation to assess the effect on leukocyte recruitment and function, as well as on inflammation resolution. The compound screen in zebrafish identified inhibitors of inflammation, prohibiting, for example, synthesis of the universal wound signal nitric oxide. Additionally, the consortium developed novel methods for visualising the emergence of reactive oxygen species, other important mediators of inflammation. Moreover, proteomic analysis of neutrophils before and after inflammation led to the discovery of 48 differentially regulated proteins. Among others, these proteins were associated with immune-related processes such as antigen presentation, chemotaxis and cytokine signalling. Collectively, INFLAM validated and further improved the zebrafish model for immune studies. Through the development of automated and more sophisticated methods for screening inflammation, it provided fundamental insight into the process. Watch the project’s video here.
Keywords
Inflammation, zebrafish, regulation of inflammation, proteomic analysis
