Leukocyte adhesion deficiencies

Ann N Y Acad Sci. 2012 Feb:1250:50-5. doi: 10.1111/j.1749-6632.2011.06389.x. Epub 2012 Jan 25.

Abstract

Leukocyte trafficking from the blood stream to tissues is essential for continuous surveillance of foreign antigens. This dynamic process, designated as the leukocyte adhesion cascade, involves distinct steps. In leukocyte adhesion deficiency (LAD) I the firm adhesion of leukocyte to the endothelium is defective, due to mutations in the beta 2 integrin gene. LAD II is caused by mutations in the fucose transporter specific to the Golgi apparatus, leading to the absence of Sialyl Lewis X-the fucosylated ligand for the selectins-thus affecting the rolling phase, the first phase of the cascade. In LAD III, a primary activation defect occurs in beta integrins 1, 2, and 3. Recently, the genetic basis for LAD III has been revealed to involve mutations in kindlin-3, a newly recognized essential component of integrin activation-the second phase of the adhesion cascade. Until now, no human or animal models of defect in transmigration-the fourth and last phase of the cascade-has been described.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Endothelium / immunology
  • Endothelium / pathology
  • Golgi Apparatus / genetics
  • Golgi Apparatus / immunology
  • Humans
  • Integrin beta Chains / genetics
  • Integrin beta Chains / immunology
  • Leukocyte Rolling / genetics*
  • Leukocyte Rolling / immunology*
  • Leukocyte-Adhesion Deficiency Syndrome / genetics*
  • Leukocyte-Adhesion Deficiency Syndrome / immunology*
  • Leukocyte-Adhesion Deficiency Syndrome / pathology
  • Leukocytes / immunology*
  • Leukocytes / pathology
  • Lewis X Antigen / genetics
  • Lewis X Antigen / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Sialyl Lewis X Antigen

Substances

  • Carrier Proteins
  • FERMT3 protein, human
  • Integrin beta Chains
  • Lewis X Antigen
  • Membrane Proteins
  • Neoplasm Proteins
  • Sialyl Lewis X Antigen