title: The molecular basis of leukocyte recruitment and its deficiencies.
abstract: The innate immune system responds to inflammation, infection and injury by recruiting neutrophils and other leukocytes. These cells are able to leave the intravascular compartment in a process called leukocyte recruitment. This process involves several distinct steps: selectin-mediated rolling, firm adhesion via integrins, postarrest modifications including adhesion strengthening and leukocyte crawling and finally transmigration into tissue. Genetic defects affecting the different steps of the cascade can result in severe impairment in leukocyte recruitment. So far, three leukocyte adhesion deficiencies (LAD I-III) have been described in humans. These LADs are rare autosomal recessive inherited disorders and, although clinically distinct, exhibit several common features including recurrent bacterial infections and leukocytosis. In LAD-I, mutations within the β2-integrin gene result in a severe defect in β2 integrin-mediated firm leukocyte adhesion. Defects in the posttranslational fucosylation of selectin ligands dramatically reduce leukocyte rolling and lead to LAD-II. Finally, LAD-III, also known as LAD-I variant, is caused by impaired integrin activation due to mutations within the kindlin-3 gene. This review provides an overview on the molecular basis of leukocyte adhesion and its deficiencies.
authors.affiliation: Walter Brendel Center for Experimental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schmidt
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Markus
authors.initials: M
authors.lastname: Sperandio
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000502:physiology; D006801:Humans; D007960:Leukocyte Disorders / Q000209:etiology / Q000235:genetics*; D036904:Leukocyte Rolling / Q000235:genetics / Q000276:immunology; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*
chemical_list: D018821:CD18 Antigens