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

Sofia de Oliveira, Constantino C. Reyes-Aldasoro, Sergio Candel, Stephen A. Renshaw, Victoriano Mulero and Ângelo Calado
J Immunol March 18, 2013, 1203266; DOI: https://doi.org/10.4049/jimmunol.1203266
Sofia de Oliveira
*Unidade de Biologia Microvascular e Inflamação, Instituto de Medicina Molecular, Instituto de Bioquímica, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;
†Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain;
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Constantino C. Reyes-Aldasoro
‡Biomedical Engineering Research Group, School of Engineering and Design, University of Sussex, Brighton BN1 9QT, United Kingdom; and
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Sergio Candel
†Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain;
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Stephen A. Renshaw
§Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, United Kingdom
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Victoriano Mulero
†Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain;
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Ângelo Calado
*Unidade de Biologia Microvascular e Inflamação, Instituto de Medicina Molecular, Instituto de Bioquímica, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;
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Abstract

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.

Footnotes

  • This work was supported by Fundação para a Ciência e Tecnologia via Ph.D. Fellowship Grant SFRH/BD/62674/2009 (to S.d.O.), Spanish Ministry of Science and Innovation through Grants BIO2011-23400 and CSD2007-00002 cofunded with the Fondo Europeo de Desarrollo Regional/European Regional Developmental Fund (to V.M.) and a Ph.D. fellowship (to S.C.), and by Fundación Séneca-Murcia via Grant 04538/GERM/06 (to V.M.). S.A.R. is funded by U.K. Medical Research Council Senior Clinical Fellowship G0701932 and Medical Research Council Centre Grant G0700091.

  • The sequence presented in this article has been submitted to the European Nucleotide Archive (http://www.ebi.ac.uk/ena/) under accession number HF674400.

  • The online version of this article contains supplemental material.

  • Received November 28, 2012.
  • Accepted February 19, 2013.
  • Copyright © 2013 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 209 (3)
The Journal of Immunology
Vol. 209, Issue 3
1 Aug 2022
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Cxcl8 (IL-8) Mediates Neutrophil Recruitment and Behavior in the Zebrafish Inflammatory Response
Sofia de Oliveira, Constantino C. Reyes-Aldasoro, Sergio Candel, Stephen A. Renshaw, Victoriano Mulero, Ângelo Calado
The Journal of Immunology March 18, 2013, 1203266; DOI: 10.4049/jimmunol.1203266

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Cxcl8 (IL-8) Mediates Neutrophil Recruitment and Behavior in the Zebrafish Inflammatory Response
Sofia de Oliveira, Constantino C. Reyes-Aldasoro, Sergio Candel, Stephen A. Renshaw, Victoriano Mulero, Ângelo Calado
The Journal of Immunology March 18, 2013, 1203266; DOI: 10.4049/jimmunol.1203266
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