Topographic requirements and dynamics of signaling via L-selectin on neutrophils

Chad E. Green, David N. Pearson, Nadine B. Christensen, Scott I. Simon

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Cross-linking of L-selectin on leukocytes signals phosphorylation of mitogen-activated protein kinases (MAPKs) leading to activation of CD18 function and enhanced transmigration on inflamed endothelium. We examined how alterations in the topography of L-selectin correlate with the dynamics of CD18 activation and phosphorylation of MAPK. Simultaneous ligation of humanized antibodies DREG55 and DREG200 provided a strategy for regulating the extent of cross-linking. Triggering of CD11b/CD18 upregulation and adhesion required clustering of L-selectin to microvillus-sized patches of ∼0.2 μm2. Immunofluorescence revealed that L-selectin was colocalized with high-affinity CD18. Anti-L-selectin-coated protein A microspheres indicated that a single site of contact to a 5.5-μm bead, or multiple contacts to 0.94- or 0.3-μm beads, elicited maximum neutrophil activation. Adhesion signaled via L-selectin coincided with the kinetics of MAPK phosphorylation and was inhibited by blocking p38 or p42/44 activity. These data demonstrate the capacity of L-selectin to transduce signals effecting rapid (∼1 s) neutrophil adhesion that is regulated by the size and frequency of receptor clustering.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number3 53-3
StatePublished - Mar 1 2003

Keywords

  • Adhesion molecules
  • Antibodies
  • Cellular activation
  • Protein kinases

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Green, C. E., Pearson, D. N., Christensen, N. B., & Simon, S. I. (2003). Topographic requirements and dynamics of signaling via L-selectin on neutrophils. American Journal of Physiology - Cell Physiology, 284(3 53-3).