Cxcl8 (IL-8) Mediates Neutrophil Recruitment and Behavior in the Zebrafish Inflammatory Response

Abstract

Neutrophils play a pivotal role in the innate immune response. The small cytokine CXCL8 (also known as interleukin-8 or IL-8) is known to be one of the most potent chemoattractant molecules which, 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 homologue, zebrafish has two distinct CXCL8 homologues: Cxcl8-l1 and Cxcl8-l2. Cxcl8-l1 is known to be up-regulated under inflammatory conditions caused by bacterial or chemical insult but until now, the role of Cxcl8s in neutrophil recruitment has not been studied. Here, we show that both Cxcl8 genes are up-regulated 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 to control neutrophils, although the directionality was not affected. Our analysis suggests that zebrafish may possess a sub-population 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.

Gcsf-Chr19 Promotes Neutrophil Migration to Damaged Tissue through Blood Vessels in Zebrafish

“…Likewise, the mRNA levels of cxcl8-l1 were also measured, given its known role in the regulation of neutrophil migration to the wound (12,14). Specifically, the transcriptional levels of these two genes were monitored by quantitative (q) PCR at 0.5, 1, 2, and 3 h after the injury was performed.…”

“…In fish, information is limited on how the output of neutrophils from the caudal hematopoietic tissue (CHT), equivalent to the mammalian fetal liver (10), is regulated. Two recent reports that used zebrafish as a model organism shed some light onto this process (11,12). In both studies, the researchers came to the same conclusion: the migration of neutrophils to a wound is dependent on the presence of Cxcl8 and Cxcr2.…”

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE) 

“…response [22,23]. FGF2 is a growth factor implicated in various biological processes such as wound healing, tumour growth and angiogenesis [24,25].…”

Microfluidic environment and tracking analysis for the observation of Artemia Franciscana

“…ObjectTrack provides numerous statistical measurements such as average distance and maximum distance per track. Statistical measure like these ones have previously been used to measure neutrophil recruitment and behaviour [12], [13]. The tracking algorithm was compared against ICY [14] in [6] with comparable results A measurement of particular interest for the analysis of Artemia is the number of complete 360-degree turns an individual can describe.…”