title: Leukocyte migration is regulated by L-selectin endoproteolytic release.
abstract: L-selectin mediates lymphocyte migration to peripheral lymph nodes and leukocyte rolling on vascular endothelium during inflammation. One unique feature that distinguishes L-selectin from other adhesion molecules is that it is rapidly cleaved from the cell surface after cellular activation. The biological significance of L-selectin endoproteolytic release was determined by generating gene-targeted mice expressing a modified receptor that was not cleaved from the cell surface. Blocking L-selectin cleavage on antigen-stimulated lymphocytes allowed their continued migration to peripheral lymph nodes and inhibited their short-term redirection to the spleen. Blocking homeostatic L-selectin cleavage also resulted in a constitutive 2-fold increase in overall L-selectin expression by leukocytes. As a result, neutrophils entered the inflamed peritoneum in greater numbers or for a longer duration. Thus, endoproteolytic cleavage regulates both homeostatic and activation-induced changes in cell surface L-selectin density, which directs the migration patterns of activated lymphocytes and neutrophils in vivo.
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Guglielmo M
authors: GM
authors: Venturi
authors: LiLi
authors: L
authors: Tu
authors: Takafumi
authors: T
authors: Kadono
authors: Adil I
authors: AI
authors: Khan
authors: Yoko
authors: Y
authors: Fujimoto
authors: Philip
authors: P
authors: Oshel
authors: Cheryl B
authors: CB
authors: Bock
authors: Ann S
authors: AS
authors: Miller
authors: Ralph M
authors: RM
authors: Albrecht
authors: Paul
authors: P
authors: Kubes
authors: Douglas A
authors: DA
authors: Steeber
authors: Thomas F
authors: TF
authors: Tedder
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism*; D018390:Gene Targeting; D019041:L-Selectin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity
chemical_list: D019041:L-Selectin; D010450:Endopeptidases