Chemokine-triggered microtubule polymerization promotes neutrophil chemotaxis and invasion but not transendothelial migration.

Yadav, Sandeep Kumar; Stojkov, Darko; Feigelson, Sara W; Roncato, Francesco; Simon, Hans-Uwe; Yousefi, Shida; Alon, Ronen (2019). Chemokine-triggered microtubule polymerization promotes neutrophil chemotaxis and invasion but not transendothelial migration. Journal of leukocyte biology, 105(4), pp. 755-766. Society for Leukocyte Biology 10.1002/JLB.3A1118-437RR

[img] Text
Simon_Chemokine-triggered microtubule polymerization promotes neutrophil.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (2MB) | Request a copy

Microtubules (MTs) are critically involved in the transport of material within cells, but their roles in chemotactic leukocyte motility and effector functions are still obscure. Resting neutrophils contain few MTs assembled in an MT organizing center (MTOC) behind their multilobular nuclei. Using a probe of real-time tubulin polymerization, SiR-tubulin, we found that neutrophils elongated their MTs within minutes in response to signals from the two prototypic chemotactic peptides, CXCL1 and fMLP. Taxol, a beta-tubulin binding and MT stabilizing drug, was found to abolish this CXCL1- and fMLP-stimulated MT polymerization. Nevertheless, taxol treatment as well as disruption of existing and de novo generated MTs did not impair neutrophil protrusion and squeezing through IL-1β-stimulated endothelial monolayers mediated by endothelial deposited CXCL1 and neutrophil CXCR2. Notably, CXCL1-dependent neutrophil TEM was not associated with neutrophil MT polymerization. Chemokinetic neutrophil motility on immobilized CXCL1 was also not associated with MT polymerization, and taxol treatment did not interfere with this motility. Nevertheless, and consistent with its ability to suppress MT polymerization induced by soluble CXCL1 and fMLP, taxol treatment inhibited neutrophil chemotaxis toward both chemotactic peptides. Taxol treatment also suppressed CXCL1- and fMLP-triggered elastase-dependent neutrophil invasion through collagen I barriers. Collectively, our results highlight de novo chemoattractant-triggered MT polymerization as key for neutrophil chemotaxis and elastase-dependent invasion but not for chemotactic neutrophil crossing of inflamed endothelial barriers.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Stojkov, Darko; Simon, Hans-Uwe and Yousefi, Shida

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0741-5400

Publisher:

Society for Leukocyte Biology

Language:

English

Submitter:

Sabrina Cookman

Date Deposited:

21 May 2019 09:30

Last Modified:

05 Mar 2020 11:24

Publisher DOI:

10.1002/JLB.3A1118-437RR

PubMed ID:

30802327

Uncontrolled Keywords:

Inflammation chemokines chemotaxis cytoskeleton migration

BORIS DOI:

10.7892/boris.127460

URI:

https://boris.unibe.ch/id/eprint/127460

Actions (login required)

Edit item Edit item
Provide Feedback