X. Li et al., REGULATION OF L-SELECTIN-MEDIATED ROLLING THROUGH RECEPTOR DIMERIZATION, The Journal of experimental medicine, 188(7), 1998, pp. 1385-1390
L-selectin binding activity for its ligand expressed by vascular endot
helium is rapidly and transiently increased after leukocyte activation
. To identify mechanisms for upregulation and assess how this influenc
es leukocyte/endothelial cell interactions, cell-surface dimers of L-s
electin were induced using the coumermycin-GyrB dimerization strategy
for cross-linking L-selectin cytoplasmic domains in L-selectin cDNA-tr
ansfected lymphoblastoid cells. Coumermycin-induced L-selectin dimeriz
ation resulted in an approximately fourfold increase in binding of pho
sphomanan monoester core complex (PPME), a natural mimic of an L-selec
tin ligand, comparable to that observed after leukocyte activation. Mo
reover, L-selectin dimerization significantly increased (by similar to
700%) the number of lymphocytes rolling an vascular endothelium under
a broad range of physiological sheer stresses, and significantly slow
ed their rolling velocities. Therefore, L-selectin dimerization may ex
plain 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 ol
igomerization may also be a common mechanism for rapidly upregulating
the adhesive or ligand-binding function of other cell-surface receptor
s.