Neutrophil Reverse Migration Becomes Transparent with Zebrafish

Starnes, Taylor W.; Huttenlocher, Anna

doi:10.1155/2012/398640

Cited by 48 publications

(37 citation statements)

References 77 publications

(128 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In view of this, we first addressed the expression of both zebrafish cxcl8 at different time points in 3 dpf Tg(mpx:gfp)i114 larvae under acute inflammatory conditions using quantitative PCR (qPCR). In this study, we made use of the tail fin transection model, a validated model to investigate acute inflammation (16)(17)(18)(19)(20)(21)(22)(23). We found that the mRNA levels of cxcl8-l1 and cxcl8-l2 were significantly increased in injured tail fin tissue and peaked at 1 hpw (Fig.…”

Section: Resultsmentioning

confidence: 88%

See 1 more Smart Citation

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

Oliveira

Reyes-Aldasoro

Candel

et al. 2013

The Journal of Immunology

314

260

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 88%

“…Additionally, the optical transparency of zebrafish and the development of fluorescent cell-specific transgenic lines have enabled the in vivo study of leukocyte biology (14,15). Zebrafish neutrophils have now been extensively studied in inflammation (16)(17)(18)(19)(20)(21)(22)(23), infection (24)(25)(26)(27), and tumor progression (28)(29)(30).…”

mentioning

confidence: 99%

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

Oliveira

Reyes-Aldasoro

Candel

et al. 2013

The Journal of Immunology

314

260

View full text Add to dashboard Cite

show abstract

“…Resolution of inflammation is an essential step during wound repair (Starnes and Huttenlocher, 2012). In some human diseases, like pyoderma gangrenosum, inflammation fails to resolve, contributing to chronic wounds and tissue damage (Powell et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

et al. 2015

Self Cite

View full text Add to dashboard Cite

Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.

show abstract

“…Neutrophil removal is commonly thought to occur exclusively through engulfment by macrophages. 9,10 However, emerging results from live imaging of embryonic zebrafish suggest that neutrophils can also reverse migrate away from sites of inflammation 11-14 , a process that can be modulated by various mediators and compounds. 15,16 …”

Section: Introductionmentioning

confidence: 99%

Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation

Hamza

Irimia

2015

Lab Chip

View full text Add to dashboard Cite

Appropriate inflammatory responses to wounds and infections require adequate numbers of neutrophils arriving at injury sites. Both insufficient and excessive neutrophil recruitment can be detrimental, favouring systemic spread of microbes or triggering severe tissue damage. Despite its importance in health and disease, the trafficking of neutrophils through tissues remains difficult to control and the mechanisms regulating it are insufficiently understood. These mechanisms are also complex and difficult to isolate using traditional in vivo models. Here we designed a microfluidic model of tissue infection/inflammation, in which human neutrophils emerge from a droplet-size samples of whole blood and display bi-directional traffic between this and micro-chambers containing chemoattractant and microbe-like particles. Two geometrical barriers restrict the entrance of red blood cells from the blood to the micro-chambers and simulate the mechanical function of the endothelial barrier separating the cells in blood from cells in tissues. We found that in the presence of chemoattractant, the number of neutrophils departing the chambers by retrotaxis is in dynamic equilibrium with the neutrophils recruited by chemotaxis. We also found that in the presence of microbe-like particles, the number of neutrophils trapped in the chambers is proportional to the number of particles. Together, the dynamic equilibrium between migration, reversed-migration and trapping processes determine the optimal number of neutrophils at a site. These neutrophils are continuously refreshed and responsive to the number of microbes. Further studies using this infection-inflammation-on-a-chip-model could help study the processes of inflammation resolution. The new in vitro experimental tools may also eventually help testing new therapeutic strategies to limit neutrophil accumulation in tissues during chronic inflammation, without increasing the risk for infections.

show abstract

Neutrophil Reverse Migration Becomes Transparent with Zebrafish

Cited by 48 publications

References 77 publications

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

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

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

Whole blood human neutrophil trafficking in a microfluidic model of infection and inflammation

Contact Info

Product

Resources

About