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L-Selectin Shedding Regulates Leukocyte Recruitment

The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration b...

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Detalles Bibliográficos
Autores principales: Hafezi-Moghadam, Ali, Thomas, Kennard L., Prorock, Alyson J., Huo, Yuqing, Ley, Klaus
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193368/
https://www.ncbi.nlm.nih.gov/pubmed/11283159
Descripción
Sumario:The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1–dependent mechanism. We examined the quality of leukocyte rolling and L-selectin–mediated signaling. Blockade of L-selectin shedding significantly reduced the “jerkiness” of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1–conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice.