uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Increased vascular permeability facilitates vascular influx of chemokines and accelerates recruitment of circulating neutrophils
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. (Mia Phillipson)ORCID iD: 0000-0003-2232-2871
Department of Microbiology and Immunology, Laboratory of Molecular Immunology, Rega Institute Leuven, Belgium. (Paul Proost)
Department of Microbiology and Immunology, Laboratory of Molecular Immunology, Rega Institute Leuven, Belgium. (Paul Proost)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. (Mia Phillipson)
(English)Manuscript (preprint) (Other academic)
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-265202OAI: oai:DiVA.org:uu-265202DiVA: diva2:866163
Available from: 2015-11-01 Created: 2015-10-25 Last updated: 2016-01-13
In thesis
1. A close-up on neutrophils: Visualizing the mechanisms of their in vivo recruitment and function
Open this publication in new window or tab >>A close-up on neutrophils: Visualizing the mechanisms of their in vivo recruitment and function
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A successful immune response depends on prompt and sufficient recruitment of leukocytes from the circulation to infected or injured sites. Mobilization of leukocytes to hypoxic tissues is vital for angiogenesis, i.e. the formation of new blood vessels from preexisting vasculature, and thus crucial for tissue growth and regeneration. Deviations from normal leukocyte recruitment drive a variety of pathologies, including chronic inflammation, autoimmune diseases and cancer, for which therapeutic options are limited or unspecific. Understanding the mechanisms by which the body controls leukocyte recruitment is therefore critical for the development of novel therapeutic strategies.

The present investigations focused on delineating the mechanisms behind leukocyte mobilization from the bloodstream to afflicted sites, by means of in vivo imaging techniques and in vitro assays. We demonstrate that, in response to inflammation, increased vascular permeability enhances transendothelial transport of tissue-released chemokines. Within the vasculature, chemokines form a chemotactic gradient sequestered on heparan sulfate, which directs crawling neutrophils and expedites their extravasation to the inflamed tissue. Consequently, gradient formation grants efficient bacterial clearance. Citrullination of chemokines by leukocyte-derived PAD enzymes in the inflamed tissue prevents chemokine transport into blood vessels, which dampens further neutrophil recruitment and thereby controls the amplitude of the inflammatory response. Moreover, the mechanisms of neutrophil recruitment in response to proangiogenic factors released during hypoxia are revealed to differ from those observed during classical inflammation. Particularly, VLA-4 integrin and VEGFR1 expressed on a defined subset of neutrophils, along with endothelial VEGFR2, are required for efficient neutrophil recruitment to hypoxia. Rather than stimulus-induced phenotypic changes on neutrophils, specific neutrophil subtypes with innate proinflammatory or proangiogenic functions (respectively, CD49d-VEGFR1lowCXCR4low and CD49d+VEGFR1highCXCR4high) coexist in the circulation of humans and mice.

In summary, this dissertation provides relevant information on specific steps of neutrophil recruitment to inflamed or hypoxic tissues, which may represent future means to down-regulate aberrant immune responses during chronic inflammation and autoimmune diseases; to increase angiogenesis during ischemia; or to limit pathological angiogenesis, a characteristic of tumor growth and of several chronic inflammatory disorders.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 56 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1159
Keyword
angiogenesis, chemokine, chemotactic gradient, citrullination, hypoxia, inflammation, intraluminal crawling, intravital imaging, PAD enzymes, permeability, proangiogenic, proinflammatory
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-265203 (URN)978-91-554-9401-8 (ISBN)
Public defence
2015-12-18, A1:107a, Biomedicinskt Centrum, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2015-11-26 Created: 2015-10-25 Last updated: 2016-01-13

Open Access in DiVA

No full text

Authority records BETA

Massena, Sara

Search in DiVA

By author/editor
Massena, Sara
By organisation
Integrative Physiology
Physiology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 322 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf