Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency

J Leukoc Biol. 2002 Oct;72(4):650-6.

Abstract

beta2 Integrins (CD18) are required for leukocyte migration. In fact, the absence of CD18 results in type-1 leukocyte adhesion deficiency (LAD-1). We analyzed the distribution phenotype and function of dendritic cells (DCs) in three LAD-1 patients with homozygous mutations of CD18. Two of them did not express CD18 (Patients A and C), and the other subject (Patient B) displayed reduced expression of beta2 integrins because of a missense mutation. Analysis of DCs derived from Patients A and B showed an abnormal morphology and a severe impairment in transendothelial migration and chemotactic response to CCL19/macrophage inflammatory protein-3beta, suggesting that CD18 is required for migration of monocyte-derived DCs. Nevertheless, DCs displayed normal macropinocytosis and underwent normal maturation after addition of tumor necrosis factor alpha. Finally, immunohistochemical analysis of lymph nodes from subjects B and C revealed a significant reduction in the number of factor-XIIIa(+) interstitial DCs in the interfollicular area in both patients, suggesting that CD18 plays a role in the migration of these cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD18 Antigens / biosynthesis
  • CD18 Antigens / immunology*
  • Cell Division
  • Cell Movement*
  • Child
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Endothelium
  • Factor XIIIa / analysis
  • Factor XIIIa / immunology
  • Humans
  • Leukocyte-Adhesion Deficiency Syndrome / blood
  • Leukocyte-Adhesion Deficiency Syndrome / genetics
  • Leukocyte-Adhesion Deficiency Syndrome / immunology*
  • Lymph Nodes / immunology
  • Monocytes / cytology
  • Monocytes / immunology
  • Monocytes / physiology

Substances

  • CD18 Antigens
  • Factor XIIIa