Leukocyte adhesion deficiency type II

Biochim Biophys Acta. 1999 Oct 8;1455(2-3):193-204. doi: 10.1016/s0925-4439(99)00071-x.

Abstract

Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persistent leukocytosis, and severe mental and growth retardation. LAD II neutrophils are deficient in expression of selectin ligand activity, and exhibit a correspondingly diminished ability to roll on endothelium and to traffic to inflammatory sites in vivo. LAD II patients exhibit a deficiency in the expression of cell surface fucosylated glycan structures that include the H and Lewis blood group determinants and the sialyl Lewis x epitope, yet the corresponding fucosyltransferase activities responsible for synthesis of these structures are expressed at normal levels. The molecular defect in LAD II has been localized to the pathway that synthesizes GDP-fucose from GDP-mannose. However, the two known component enzymes in this GDP-fucose biosynthetic pathway are normal in sequence and in expression levels in LAD II cells. The genetic lesion in LAD II that accounts for the generalized fucosylation defect in LAD II patients remains to be determined.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ABO Blood-Group System / chemistry
  • ABO Blood-Group System / immunology
  • Animals
  • Cell Adhesion Molecules / immunology
  • Cell Line
  • Cell Movement
  • Fucose / metabolism
  • Fucosyltransferases / metabolism
  • Guanosine Diphosphate Fucose / biosynthesis
  • Guanosine Diphosphate Mannose / metabolism
  • Humans
  • Hydro-Lyases / antagonists & inhibitors
  • Hydro-Lyases / metabolism
  • Leukocyte-Adhesion Deficiency Syndrome / genetics*
  • Leukocyte-Adhesion Deficiency Syndrome / immunology
  • Leukocyte-Adhesion Deficiency Syndrome / metabolism
  • Leukocytes / immunology
  • Lewis Blood Group Antigens / chemistry
  • Lewis Blood Group Antigens / immunology
  • Lymphocytes / immunology
  • Neutrophils / immunology
  • Phenotype
  • Selectins / metabolism

Substances

  • ABO Blood-Group System
  • Cell Adhesion Molecules
  • Lewis Blood Group Antigens
  • Selectins
  • Guanosine Diphosphate Fucose
  • Fucose
  • Guanosine Diphosphate Mannose
  • Fucosyltransferases
  • Hydro-Lyases