Molecular analysis of human leukocyte adhesion deficiency

概要

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The normal response of the immune system to infections of the skin or mucosal tissues requires the ability of peripheral blood leukocytes to mobilize to the site of infection. In a classical inflammatory reaction, neutrophils and monocytes migrate in response to chemotactic factors released at the infection site. However, until recently, the molecular mechanisms which enable leukocytes to migrate across blood vessels have been largely unknown. These mechanisms have been elucidated, in part, by the characterization of a recently defined disease called human leukocyte adhesion deficiency (LAD). Patients with this heritable disease suffer from severe recurrent bacterial and fungal infections of soft tissues, primarily skin and mucous membranes. Infected, necrotic lesions in these patients contain few leukocytes despite the observation that these patients have chronic leukocytosis. In the early 1980s, several laboratories demonstrated that this disease is due to a cell surface deficiency of the LFA-1, Mac-1, and p150, 95 family of leukocyte adhesion proteins. More recently we have shown that LAD is due to heterogenous mutations in the β subunit common to the all three of these leukocyte glycoproteins. Although LAD is a rare disease, the analysis of this disease has greatly increased our understanding of the biology of the leukocyte adhesion proteins and the molecular mechanisms involved in the immune response to infections of the skin.