TY - JOUR
T1 - Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency
AU - Fiorini, Maurilia
AU - Vermi, William
AU - Facchetti, Fabio
AU - Moratto, Daniele
AU - Alessandri, Giulio
AU - Notarangelo, Lucia
AU - Caruso, Arnaldo
AU - Grigolato, Piergiovanni
AU - Ugazio, Alberto G.
AU - Notarangelo, Luigi D.
AU - Badolato, Raffaele
PY - 2002/10/1
Y1 - 2002/10/1
N2 - β2 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 β2 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-β3, 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 α. 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.
AB - β2 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 β2 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-β3, 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 α. 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.
KW - Adhesion molecules
KW - Cell trafficking
KW - Human
KW - Immunodeficiency diseases
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M3 - Article
C2 - 12377933
AN - SCOPUS:0036826734
VL - 72
SP - 650
EP - 656
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 4
ER -