title: A functional role for circulating mouse L-selectin in regulating leukocyte/endothelial cell interactions in vivo.
abstract: L-selectin mediates the initial capture and subsequent rolling of leukocytes along inflamed vascular endothelium and mediates lymphocyte migration to peripheral lymphoid tissues. Leukocyte activation induces rapid endoproteolytic cleavage of L-selectin from the cell surface, generating soluble L-selectin (sL-selectin). Because human sL-selectin retains ligand-binding activity in vitro, mouse sL-selectin and its in vivo relevance were characterized. Comparable with humans, sL-selectin was present in adult C57BL/6 mouse sera at approximately 1.7 micro g/ml. Similar levels of sL-selectin were present in sera from multiple mouse strains, despite their pronounced differences in cell surface L-selectin expression levels. Adhesion molecule-deficient mice prone to spontaneous chronic inflammation and mice suffering from leukemia/lymphoma had 2.5- and 20-fold increased serum sL-selectin levels, respectively. By contrast, serum sL-selectin levels were reduced by 70% in Rag-deficient mice lacking mature lymphocytes. The majority of serum sL-selectin had a molecular mass of 65-75 kDa, consistent with its lymphocyte origin. Slow turnover may explain the relatively high levels of sL-selectin in vivo. The t(1/2) of sL-selectin, assessed by transferring sera from wild-type mice into L-selectin-deficient mice and monitoring serum sL-selectin levels by ELISA, was >20 h, and it remained detectable for longer than 1 wk. Short-term in vivo lymphocyte migration assays demonstrated that near physiologic levels ( approximately 0.9 micro g/ml) of sL-selectin decreased lymphocyte migration to peripheral lymph nodes by >30%, with dose-dependent inhibition occurring with increasing sL-selectin concentrations. These results suggest that sL-selectin influences lymphocyte migration in vivo and that the increased sL-selectin levels present in certain pathologic conditions may adversely affect leukocyte migration.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: LiLi
authors.initials: L
authors.lastname: Tu
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Guglielmo M
authors.initials: GM
authors.lastname: Venturi
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D019041:L-Selectin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000097:blood
chemical_list: D015815:Cell Adhesion Molecules; D020033:Protein Isoforms; D019041:L-Selectin