Leukocyte migration is regulated by L-selectin endoproteolytic release.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Venturi, GM; Tu, L; Kadono, T; Khan, AI; Fujimoto, Y; Oshel, P; Bock, CB; Miller, AS; Albrecht, RM; Kubes, P; Steeber, DA; Tedder, TF

Published Date

  • November 2003

Published In

Volume / Issue

  • 19 / 5

Start / End Page

  • 713 - 724

PubMed ID

  • 14614858

Pubmed Central ID

  • 14614858

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(03)00295-4

Language

  • eng