The maximum dose of interleukin 2 (IL-2) alone or with adoptively transferred lymphocytes is limited by the vascular leak syndrome, re sulting from an increase in vascular permeability. Using intravital mi croscopy to quantify cell interaction in vivoand the Miles assay to assess changes in vascular permeability, we have shown that II-2 increases both leukocyte-endothelial cell adhesion and vas...

The maximum dose of interleukin 2 (IL-2) alone or with adoptively transferred lymphocytes is limited by the vascular leak syndrome, resulting from an increase in vascular permeability. Using intravital microscopy to quantify cell interaction in vivo and the Miles assay to assess changes in vascular permeability, we have shown that IL-2 increases both leukocyte-endothelial cell adhesion and vasc...

alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate he...

This paper presents a case of the moderate form of Leukocyte adhesion deficiency type 1 (LAD-1) in a 4 year-old boy. LAD-1 is a rare, inherited immunodeficiency that affects 1 in 1 million people yearly. Affected patients are susceptible to recurrent bacterial and fungal infections, impaired pus formation and delayed wound healing. In the oral clinical finding, more important is a generalized p...

Tissue-specific silencing of genes may be used for genetic engineering in mice and has possible therapeutic applications in humans. Current strategies in mice rely on Cre/loxP technology requiring the generation of multiple transgenic lines and breeding strategies. Here, we describe the selective silencing of CD18, a leukocyte-specific integrin in neutrophils using a micro RNA (miRNA) strategy ...

Leukocyte adhesion deficiency/congenital disorder of glycosylation IIc (LAD II/CDG IIc) is a genetic disease characterized by a decreased expression of fucose in glycoconjugates, resulting in leukocyte adhesion deficiency and severe morphological and neurological abnormalities. The biochemical defect is a reduced transport of guanosine diphosphate-L-fucose (GDP-L-fucose) from cytosol into the G...

Recently, we reported a rare leukocyte adhesion deficiency (LAD) associated with severe defects in integrin activation by chemokine signals, despite normal ligand binding of leukocyte integrins.(1) We now report that the small GTPase, Rap1, a key regulator of inside-out integrin activation is abnormally regulated in LAD Epstein-Barr virus (EBV) lymphocyte cells. Both constitutive and chemokine-...

Leukocyte Adhesion Deficiency I (LAD-I) is a primary immunodeficiency caused by single gene mutations in the CD18 subunit of β2 integrins which result in defective transmigration of neutrophils into the tissues. Affected patients suffer from recurrent life threatening infections and severe oral disease (periodontitis). Microbial communities in the local environment (subgingival plaque) are thou...

MRL/fas(lpr) mice, which undergo a systemic autoimmune disease with similarities to systemic lupus erythematosus (SLE), display reduced pathology and prolonged survival if rendered deficient in ICAM-1. However, it remains unclear whether this is a result of the ability of ICAM-1 to promote the immune response or mediate leukocyte recruitment. Therefore, the aim of these studies was to compare t...