title: Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency.
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.
authors.affiliation: Istituto di Medicina Molecolare Angelo Nocivelli, Università di Brescia, Italy.
authors.forename: Maurilia
authors.initials: M
authors.lastname: Fiorini
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
authors.forename: Lucia
authors.initials: L
authors.lastname: Notarangelo
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Ugazio
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D018821:CD18 Antigens / Q000096:biosynthesis / Q000276:immunology*; D002455:Cell Division; D002465:Cell Movement; D002648:Child; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D004727:Endothelium; D026122:Factor XIIIa / Q000032:analysis / Q000276:immunology; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology
chemical_list: D018821:CD18 Antigens; D026122:Factor XIIIa