Leukocyte migration is regulated by L-selectin endoproteolytic release |
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Authors: | Venturi Guglielmo M Tu LiLi Kadono Takafumi Khan Adil I Fujimoto Yoko Oshel Philip Bock Cheryl B Miller Ann S Albrecht Ralph M Kubes Paul Steeber Douglas A Tedder Thomas F |
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Affiliation: | Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. |
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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. |
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