Ontogenetic regulation of leukocyte recruitment in mouse yolk sac vessels

In adult mammals, leukocyte recruitment follows a well-defined cascade of adhesion events enabling leukocytes to leave the circulatory system and transmigrate into tissue. Currently, it is unclear whether leukocyte recruitment proceeds in a similar fashion during fetal development. Considering the f...

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Main Authors: Sperandio, Markus (Author) , Quackenbush, Elizabeth J. (Author) , Sushkova, Natalia (Author) , Altstätter, Johannes (Author) , Nussbaum, Claudia (Author) , Schmid, Stephan (Author) , Pruenster, Monika (Author) , Kurz, Angela (Author) , Margraf, Andreas (Author) , Steppner, Alina (Author) , Schweiger, Natalie (Author) , Borsig, Lubor (Author) , Boross, Ildikó (Author) , Krajewski, Nele (Author) , Genzel-Boroviczény, Orsolya (Author) , Jeschke, Udo (Author) , Frommhold, David (Author) , Andrian, Ulrich H. von (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Blood
Year: 2013, Volume: 121, Issue: 21, Pages: e118-e128
ISSN:1528-0020
DOI:10.1182/blood-2012-07-447144
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2012-07-447144
Verlag, lizenzpflichtig, Volltext: https://ashpublications.org/blood/article/121/21/e118/31313/Ontogenetic-regulation-of-leukocyte-recruitment-in
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Author Notes:Markus Sperandio, Elizabeth J. Quackenbush, Natalia Sushkova, Johannes Altstätter, Claudia Nussbaum, Stephan Schmid, Monika Pruenster, Angela Kurz, Andreas Margraf, Alina Steppner, Natalie Schweiger, Lubor Borsig, Ildiko Boros, Nele Krajewski, Orsolya Genzel-Boroviczeny, Udo Jeschke, David Frommhold, and Ulrich H. von Andrian
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Summary:In adult mammals, leukocyte recruitment follows a well-defined cascade of adhesion events enabling leukocytes to leave the circulatory system and transmigrate into tissue. Currently, it is unclear whether leukocyte recruitment proceeds in a similar fashion during fetal development. Considering the fact that the incidence of neonatal sepsis increases dramatically with decreasing gestational age in humans, we hypothesized that leukocyte recruitment may be acquired only late during fetal ontogeny. To test this, we developed a fetal intravital microscopy model in pregnant mice and, using LysEGFP (neutrophil reporter) mice, investigated leukocyte recruitment during fetal development. We show that fetal blood neutrophils acquire the ability to roll and adhere on inflamed yolk sac vessels during late fetal development, whereas at earlier embryonic stages (before day E15), rolling and adhesion were essentially absent. Accordingly, flow chamber experiments showed that fetal EGFP+ blood cells underwent efficient adhesion only when they were harvested on or after E15. Fluorescence-activated cell sorter analysis on EGFP+ fetal blood cells revealed that surface expression of CXCR2 and less pronounced P-selectin glycoprotein ligand-1 (PSGL-1) begin to increase only late in fetal life. Taken together, our findings demonstrate that inflammation-induced leukocyte recruitment is ontogenetically regulated and enables efficient neutrophil trafficking only during late fetal life.
Item Description:Prepublished online as Blood First edition paper, March 22, 2013
Gesehen am 14.02.2022
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2012-07-447144