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(Journal of Leukocyte Biology. 2002;72:650-656.)
© 2002 by Society for Leukocyte Biology

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

Maurilia Fiorini^*,, William Vermi, Fabio Facchetti, Daniele Moratto^*,, Giulio Alessandri, Lucia Notarangelo^*,, Arnaldo Caruso, Piergiovanni Grigolato, Alberto G. Ugazio^*,, Luigi D. Notarangelo^*, and Raffaele Badolato^*,

^* Istituto di Medicina Molecolare "Angelo Nocivelli",
Clinica Pediatrica,
Cattedra di Anatomia Patologica, and
Istituto di Microbiologia, Università di Brescia, Italy

Correspondence: Raffaele Badolato, M.D., Ph.D., Clinica Pediatrica, Università di Brescia, c/o Spedali Civili, 25123 Brescia, Italy. E-mail: badolato{at}master.cci.unibs.it

ß2 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 ß2 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-3ß, 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 . 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.

Key Words: human • immunodeficiency diseases • adhesion molecules • cell trafficking

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