Journal
CURRENT BIOLOGY
Volume 22, Issue 24, Pages 2375-2382Publisher
CELL PRESS
DOI: 10.1016/j.cub.2012.11.018
Keywords
-
Categories
Funding
- Pasteur Foundation (USA)
- Pasteur Roux (France) fellowship program
- Agence Nationale de la Recherche (ANR) [NT05-4_41967]
- Institut National de la Recherche Agronomique (INRA)
- Wageningen University (WUR)
Ask authors/readers for more resources
Chemokines are essential in many cell migration processes, including the recruitment of leukocytes to sites of infection [1-3]. In the latter context, chemokines promote leukocyte extravasation into the relevant tissue through a well-studied cascade of events [4-9]. It is widely believed that chemokines further guide leukocytes within tissues via chemotaxis, the directed migration along gradients of soluble ligands. However, the basic mechanism of chemokine action within tissues has yet to be formally addressed in vivo. We identified a chemokine (zCxcl8) that recruits zebrafish neutrophils to infection loci and analyzed its function directly within interstitial tissues of living larvae. Using noninvasive imaging and a controlled cellular source of zCxcl8, we found that zCxcl8 guides neutrophils in a 2-fold manner: by biasing cell speed according to direction (orthotaxis) and by restricting cell motility near the source. We further show that zCxcl8 establishes tissue-bound gradients in vivo by binding to heparan sulfate proteoglycans (HSPGs). Inhibition of this interaction compromised both directional guidance and restriction of neutrophil motility. Thus, by interacting with extracellular HSPGs, chemokines establish robust surface-bound (haptotactic) gradients that mediate both recruitment and retention of leukocytes at sites of infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available