Close

Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

Janine J.G. Arts, Eike K. Mahlandt, Max L.B. Grönloh, Lilian Schimmel, Ivar Noordstra, Abraham C.I. van Steen, Simon Tol, Jos van Rijssel, Martijn A. Nolte, Marten Postma, Satya Khuon, John M. Heddleston, Eric Wait, Teng-Leong Chew, Mark Winter, Eloi Montanez, Joachim Goedhart, Jaap D. van Buul

Posted on: 19 February 2021 , updated on: 25 February 2021

Preprint posted on 21 January 2021

Article now published in eLife at http://dx.doi.org/10.7554/elife.66074

Taking a dive; neutrophils utilise protrusions in endothelial junctional membranes to transmigrate

Selected by Jonny Coates

Categories: cell biology, immunology

Background

Neutrophils are innate immune cells that are primarily responsible for phagocytosing cellular debris and invading pathogens. Neutrophils are the most abundant white blood cell in human blood and have relatively short life-spans; they are released from the bone marrow and eliminated by macrophages within the span of a single day (1).

These specialised cells are often the first to traffic to sites of injury and infection. In order to reach sites of infection, neutrophils follow chemoattractant signals and then migrate out of the blood stream and into tissues (2). This migratory cascade is outlined in figure 1. Once neutrophils reach the target tissue they must adhere to the lumen wall, a process that begins as tethering and rolling before neutrophils finally adhere to the lumen wall. Following adhesion, neutrophils transmigrate between endothelial cells (diapedesis) and penetrate the basement membrane.

Figure 1. Neutrophil adhesion cascade.

Neutrophils have been observed to exit at particular sites, sometimes termed “hotspots”. However, why neutrophils choose to exit at these sites is not well known. The authors of this preprint examined the exit sites used by neutrophils to migrate across the endothelium; applying lattice light sheet microscopy to explore why neutrophils chose particular exit sites.

 

Key findings

  1.   Leukocytes show a preference for endothelial membrane protrusions at cell junctions for transmigration

Utilising light sheet microscopy and time-lapse movies, the authors discovered endothelial junctional membrane protrusions that were used as sites of diapedesis by neutrophils. As neutrophils transmigrate following inflammatory stimuli, the authors treated tissue with TNF-α. This treatment increased the junctional membrane protrusions, enabling more neutrophil trafficking into the tissues.

 

Movie 1. Movie demonstrating neutrophils utilising JMPs for transendothelial migration

  1.   Protrusions depend on Rac1 activity

Junctional membrane protrusions were shown to be regulated by the actin cytoskeleton. To investigate this further, the authors focussed on Rac1, a small GTPase that has known roles in regulating the actin skeleton and lamellipodia formation. Activating Rac1 resulted in an induction of junctional membrane protrusions. Neutrophils then utilised these artificially created exit sites for diapedesis.

Figure 2. Summary of the main findings from the preprint. Adapted from Fig 4I in the preprint under a CC-BY 4.0 license.

 

Importance of this work / Why I selected this preprint

This preprint beautifully demonstrates the power of microscopy in uncovering novel cell behaviours that we would otherwise miss – plus you can’t beat the amazing images and videos that accompany this preprint.

 

Open questions

 

  1. The authors show JMPs in cremaster muscles, did they investigate other tissues? As it is known that the mechanism of neutrophil entry can be tissue dependent it’s possible that these protrusions are unique to specific tissues.
  2. Why do certain endothelial cells form JMPs and not others?
  3. Do all pro-inflammatory stimuli increase JMPs? What role do anti-inflammatory signals play?

 

References

  1. Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front Physiol [Internet]. 2018;9. Available from: https://www.frontiersin.org/articles/10.3389/fphys.2018.00113/full
  2. Voisin M-B, Nourshargh S. Neutrophil Transmigration: Emergence of an Adhesive Cascade within Venular Walls. J Innate Immun. 2013;5(4):336–47.

Tags: immunology, leukocyte migration, light-sheet microscopy, microscopy, protrusions, transmigration

doi: https://doi.org/10.1242/prelights.27391

Read preprint (No Ratings Yet)

Author's response

Jaap van Buul shared

  1. The authors show JMPs in cremaster muscles, did they investigate other tissues? As it is known that the mechanism of neutrophil entry can be tissue dependent it’s possible that these protrusions are unique to specific tissues.

Answer: no, we did not look at other tissue yet. This is something we are aiming at doing.

  1. Why do certain endothelial cells form JMPs and not others?

Answer: To be frank, we do not know. What we do know is that endothelial cell monolayers show a large matter of heterogeneity. For example, von Willebrand factor or ICAM-1 are highly expressed in one endothelial cell whereas the expression is drastically reduced in the neighbouring one. Why this is, is not known, but perhaps something like this is also true for cell activation.

  1. Do all pro-inflammatory stimuli increase JMPs? What role do anti-inflammatory signals play?

Answer: We have tested several inflammatory mediators, TNF, IL1B, LPS and IFN. All these stimuli induced the JMPs. We dd not combine these stimuli yet, to see if they can reinforce each other. Also, we did not test if the length of stimulus changes JMP kinetics. Something to figure out!

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the cell biology category:

Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping

Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, et al.

Selected by 06 June 2024

Bhaval Parmar

Developmental Biology

LINC complex alterations are a hallmark of sporadic and familial ALS/FTD

Riccardo Sirtori, Michelle Gregoire, Emily Potts, et al.

Selected by 03 June 2024

Megane Rayer et al.

Cell Biology

G6b-B antibody-based cis-acting platelet receptor inhibitors (CAPRIs) as a new family of anti-thrombotic therapeutics

Alexandra Mazharian, Ophélie Bertin, Amrita Sarkar, et al.

Selected by 03 June 2024

Simon Cleary

Pharmacology and Toxicology

Also in the immunology category:

Feedback loop regulation between viperin and viral hemorrhagic septicemia virus through competing protein degradation pathways

Xiaobing Lu, Meisheng Yi, Zhe Hu, et al.

Selected by 21 May 2024

UofA IMB565 et al.

Immunology

Fetal brain response to maternal inflammation requires microglia

Bridget Elaine LaMonica Ostrem, Nuria Dominguez Iturza, Jeffrey Stogsdill, et al.

Selected by 24 April 2024

Manuel Lessi

Neuroscience

Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis

Katsuyuki Nishi, Taro Sakamaki, Akiomi Nagasaka, et al.

Selected by 24 April 2024

Manuel Vicente, Anaisa Ferreira

Immunology

preLists in the cell biology category:

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage

Also in the immunology category:

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Antimicrobials: Discovery, clinical use, and development of resistance

Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.

 



List by Zhang-He Goh

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar
Close