Leukocyte migration is regulated by L-selectin endoproteolytic release.
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.
Venturi
Guglielmo M
GM
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Tu
LiLi
L
Kadono
Takafumi
T
Khan
Adil I
AI
Fujimoto
Yoko
Y
Oshel
Philip
P
Bock
Cheryl B
CB
Miller
Ann S
AS
Albrecht
Ralph M
RM
Kubes
Paul
P
Steeber
Douglas A
DA
Tedder
Thomas F
TF
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
D019041:L-Selectin; D010450:Endopeptidases