Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration
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 CoatesCategories: 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
- 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
- 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
- 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.
- Why do certain endothelial cells form JMPs and not others?
- Do all pro-inflammatory stimuli increase JMPs? What role do anti-inflammatory signals play?
References
- 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
- Voisin M-B, Nourshargh S. Neutrophil Transmigration: Emergence of an Adhesive Cascade within Venular Walls. J Innate Immun. 2013;5(4):336–47.
doi: https://doi.org/10.1242/prelights.27391
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
The RNA binding protein HNRNPA2B1 regulates RNA abundance and motor protein activity in neurites
Felipe Del Valle Batalla
Pharyngeal neuronal mechanisms governing sour taste perception in Drosophila melanogaster
Matthew Davies
Feedback regulation by the RhoA-specific GEF ARHGEF17 regulates actomyosin network disassembly
Vibha SINGH
Also in the immunology category:
Integrin conformation-dependent neutrophil slowing obstructs the capillaries of the pre-metastatic lung in a model of breast cancer
Simon Cleary
Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted
Marina Schernthanner
The bat Influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
Mitchell Sarmie, Mohammed A. Jalloh
preListscell biology category:
in theBSCB-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 |