Regulation of L-selectin-mediated rolling through receptor dimerization

Xuan Li, Douglas A. Steeber, Mimi L K Tang, Michael A. Farrar, Roger M. Perlmutter, Thomas F. Tedder

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

L-selectin binding activity for its ligand expressed by vascular endothelium is rapidly and transiently increased after leukocyte activation. To identify mechanisms for upregulation and assess how this influences leukocyte/endothelial cell interactions, cell-surface dimers of L-selectin were induced using the coumermycin-GyrB dimerization strategy for cross- linking L-selectin cytoplasmic domains in L-selectin cDNA-transfected lymphoblastoid cells. Coumermycin-induced L-selectin dimerization resulted in an approximately fourfold increase in binding of phosphomanan monoester core complex (PPME), a natural mimic of an L-selectin ligand, comparable to that observed after leukocyte activation. Moreover, L-selectin dimerization significantly increased (by ~700%) the number of lymphocytes rolling on vascular endothelium under a broad range of physiological shear stresses, and significantly slowed their rolling velocities. Therefore, L-selectin dimerization may explain the rapid increase in ligand binding activity that occurs after leukocyte activation and may directly influence leukocyte migration to peripheral lymphoid tissues or to sites of inflammation. Inducible oligomerization may also be a common mechanism for rapidly upregulating the adhesive or ligand-binding function of other cell-surface receptors.

Original languageEnglish (US)
Pages (from-to)1385-1390
Number of pages6
JournalJournal of Experimental Medicine
Volume188
Issue number7
DOIs
StatePublished - Oct 5 1998

Keywords

  • Dimerization
  • L-selectin
  • Leukocyte/endothelial interaction
  • Regulation
  • Rolling

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    Li, X., Steeber, D. A., Tang, M. L. K., Farrar, M. A., Perlmutter, R. M., & Tedder, T. F. (1998). Regulation of L-selectin-mediated rolling through receptor dimerization. Journal of Experimental Medicine, 188(7), 1385-1390. https://doi.org/10.1084/jem.188.7.1385