Swimming Against the Tide: Drugs Drive Neutrophil Reverse Migration

Abstract

Unbiased screens in transgenic zebrafish reveal drugs that resolve inflammation by driving reverse migration of neutrophils.

Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo

“…whether knocking down CDK9 affects cellular recruitment as well as neutrophil apoptosis at the injury site. It is known in zebrafish that reverse migration of neutrophils away from sites of inflammation occurs484950, a cellular behaviour also thought to occur in mammals51. It will also therefore be interesting to investigate if CDK9 is a regulator of reverse neutrophil migration, perhaps via the regulation of specific molecules known to be important in reverse migration52.…”

“…It will also therefore be interesting to investigate if CDK9 is a regulator of reverse neutrophil migration, perhaps via the regulation of specific molecules known to be important in reverse migration52. Interestingly, zebrafish neutrophil migration away from sites of wounding can be enhanced pharmacologically by treatment with the compound Tanshinone IIA, a derivative of the Chinese medicinal herb Salvia miltiorrhiza 2649. This may be another mechanism by which resolution of inflammation could be enhanced.…”

Defining the phenotype of neutrophils following reverse migration in zebrafish

“…Clearance of apoptotic neutrophils by macrophages, in turn, leads to down-regulation of macrophage phlogistic potential [33]. It is now becoming accepted that the more recently described phenomenon of reverse migration makes a significant contribution to inflammation resolution in certain contexts [34]. Therefore, a key question is whether this dissipation of the inflammatory burden is associated with any phenotypic alteration in the neutrophils themselves.…”

Atheroprotective Effects and Molecular Targets of Tanshinones Derived From Herbal Medicine Danshen

“…Studies in the past decade suggest that impaired resolution of inflammation in the vessel wall is a critical permissive element in the progression of atherosclerosis . Inflammation is a finely tuned biological process that involves multiple cell types and has the primary role of safeguarding human health . After injury occurs in the tissue, inflammatory cells such as neutrophils are guided to specific sites of injury.…”

“…After injury occurs in the tissue, inflammatory cells such as neutrophils are guided to specific sites of injury. After the initial injury is resolved, these recruited neutrophils must be cleared to eliminate inappropriate activation . Therefore, enhancing the resolution of the inflammation represents a new therapeutic strategy for treating atherosclerosis .…”