title: Ontogenetic regulation of leukocyte recruitment in mouse yolk sac vessels.
abstract: 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.
authors.affiliation: Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians Universität, Munich, Germany. markus.sperandio@med.uni-muenchen.de
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Quackenbush
authors.forename: Natalia
authors.initials: N
authors.lastname: Sushkova
authors.forename: Johannes
authors.initials: J
authors.lastname: Altstätter
authors.forename: Claudia
authors.initials: C
authors.lastname: Nussbaum
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmid
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.forename: Angela
authors.initials: A
authors.lastname: Kurz
authors.forename: Andreas
authors.initials: A
authors.lastname: Margraf
authors.forename: Alina
authors.initials: A
authors.lastname: Steppner
authors.forename: Natalie
authors.initials: N
authors.lastname: Schweiger
authors.forename: Lubor
authors.initials: L
authors.lastname: Borsig
authors.forename: Ildiko
authors.initials: I
authors.lastname: Boros
authors.forename: Nele
authors.initials: N
authors.lastname: Krajewski
authors.forename: Orsolya
authors.initials: O
authors.lastname: Genzel-Boroviczeny
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.forename: David
authors.initials: D
authors.lastname: Frommhold
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004900:Erythroblasts / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007107:Immune System / Q000166:cytology / Q000196:embryology*; D036904:Leukocyte Rolling / Q000276:immunology; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D055806:Microvessels / Q000166:cytology / Q000196:embryology* / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011247:Pregnancy; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D015017:Yolk Sac / Q000098:blood supply / Q000166:cytology / Q000196:embryology*
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D023063:Receptors, Interleukin-8B; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins