Glycosylation in the control of selectin counter‐receptor structure and function

JB Lowe - Immunological reviews, 2002 - Wiley Online Library
JB Lowe
Immunological reviews, 2002Wiley Online Library
Leukocyte trafficking is characterized by sequential cell adhesion and activation events that
deliver specific leukocyte subsets to distinct extravascular locations under different
pathophysiological circumstances. E‐, P‐and/or L‐selectin‐dependent leukocyte–
endothelial cell adhesive interactions contribute essentially to this process. Selectin counter‐
receptor activity on leukocyte and high endothelial venules is borne by specific
glycoproteins whose ability to support adhesion requires specific post‐translational …
Summary: Leukocyte trafficking is characterized by sequential cell adhesion and activation events that deliver specific leukocyte subsets to distinct extravascular locations under different pathophysiological circumstances. E‐, P‐ and/or L‐selectin‐dependent leukocyte–endothelial cell adhesive interactions contribute essentially to this process. Selectin counter‐receptor activity on leukocyte and high endothelial venules is borne by specific glycoproteins whose ability to support adhesion requires specific post‐translational modifications. These modifications are typified by serine/threonine‐linked oligosaccharides capped with the sialyl Lewis x moiety, an α2–3sialylated, α1‐3ucosylated tetrasaccharide synthesized by specific glycosyltransferases. Recent advances in glycan structure analysis and in characterizing mice with targeted deletions of glycosyltransferase and sulfotransferase genes discloses an essential role for 6‐O GlcNAc sulfate modification of the sialyl Lewis x tetrasaccharide in L‐selectin counter‐receptor activity. Related studies identify novel extended Core 1 type O‐glycans bearing the 6‐sulfosialyl Lewis x moiety, define the molecular nature of the MECA‐79 epitope, and disclose a requirement for the α1‐3fucosyltransferases FucT‐IV and FucT‐VII in the elaboration of L‐selectin counter‐receptor activities. Parallel studies also demonstrate that these 2 fucosyltransferases, a core 2 GlcNAc transferase, and core 2‐type sialyl Lewis x determinants make essential contributions to leukocyte P‐selectin counter‐receptor activity, and figure prominently in the control of leukocyte E‐selectin counter‐receptor activity.
Wiley Online Library