de Oliveira, S., Reyes-Aldasoro, C.C., Candel, S., Renshaw, S.A., Mulero, V., and Calado, A. (2013) Cxcl8 (IL-8) Mediates Neutrophil Recruitment and Behavior in the Zebrafish Inflammatory Response. Journal of immunology (Baltimore, Md. : 1950). 190(8):4349-59.
Neutrophils play a pivotal role in the innate immune response. The small cytokine CXCL8 (also known as IL-8) is known to be
one of the most potent chemoattractant molecules that, among several other functions, is responsible for guiding neutrophils
through the tissue matrix until they reach sites of injury. Unlike mice and rats that lack a CXCL8 homolog, zebrafish has
two distinct CXCL8 homologs: Cxcl8-l1 and Cxcl8-l2. Cxcl8-l1 is known to be upregulated under inflammatory conditions caused
by bacterial or chemical insult but until now the role of Cxcl8s in neutrophil recruitment has not been studied. In this study
we show that both Cxcl8 genes are upregulated in response to an acute inflammatory stimulus, and that both are crucial for
normal neutrophil recruitment to the wound and normal resolution of inflammation. Additionally, we have analyzed neutrophil
migratory behavior through tissues to the site of injury in vivo, using open-access phagocyte tracking software PhagoSight.
Surprisingly, we observed that in the absence of these chemokines, the speed of the neutrophils migrating to the wound was
significantly increased in comparison with control neutrophils, although the directionality was not affected. Our analysis
suggests that zebrafish may possess a subpopulation of neutrophils whose recruitment to inflamed areas occurs independently
of Cxcl8 chemokines. Moreover, we report that Cxcl8-l2 signaled through Cxcr2 for inducing neutrophil recruitment. Our study,
therefore, confirms the zebrafish as an excellent in vivo model to shed light on the roles of CXCL8 in neutrophil biology.