Leukocyte adhesion deficiency type-1 (LAD-1) is an autosomal recessive immunodeficiency caused by mutations in the beta2 integrin, CD18, that impair CD11/CD18 heterodimer surface expression and/or function. Absence of functional CD11/CD18 integrins on leukocytes, particularly neutrophils, leads to their incapacity to adhere to the endothelium and migrate to sites of infection. We studied 3 LAD-...

We investigated in vivo neutrophil and lymphocyte function in a patient who lacks Sialyl-Lewis-X, a ligand for the selectin family of leukocyte adhesion molecules (leukocyte adhesion deficiency II, LAD II). As assessed by skin chamber and skin window techniques, in vivo chemotaxis of neutrophils was markedly impaired (less than 6% of normal values). A marginal pool was present as determined by ...

Over the past decade, it has become clear that the specificity and targeted regulation of leukocyte trafficking result from the sequential and frequently overlapping functions of various adhesive receptors. Adhesion between the leukocyte and the vessel wall begins with repeated transient interactions that allow the leukocyte to “roll” across the endothelium at a rate lower than that of blood fl...

Leukocyte adhesion deficiency type II is a hereditary disorder of neutrophil migration caused by mutations in the guanosine diphosphate-fucose transporter gene (SLC35C1). In these patients, inability to generate key fucosylated molecules including sialyl Lewis X leads to leukocytosis and recurrent infections, in addition to short stature and developmental delay. We report two brothers with shor...

Neutrophils are the most abundant circulating leukocyte and play a fundamental role in the innate immune response. Patients with neutropenia, leukocyte adhesion deficiency syndrome or chronic granulomatous disease are particularly prone to bacterial and fungal infection. However, the highly destructive capacity of these cells also increases the potential for neutrophil damage to healthy tissues...

The leukocyte adhesion deficiency syndrome type II (LAD-II) is caused by a general defect in fucose metabolism, which leads to the absence of fucosylated sugar determinants such as the selectin ligand SLe(x). In view of the important role of selectins in lymphocyte migration and homing, we have explored the in vivo immune responsiveness and lymphocyte recruitment to the skin, in response to the...

Integrins mediate cell-cell and cell-extracellular matrix attachments. Integrins are signaling receptors because their cytoplasmic tails are docking sites for cytoskeletal and signaling proteins. Kindlins are a family of band 4.1-ezrin-radixin-moesin-containing intracellular proteins. Apart from regulating integrin ligand-binding affinity, recent evidence suggests that kindlins are involved in ...

The endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. We investigated the role of junctional adhesion molecule-A (JAM-A), a receptor expressed in endothelial tight junctions, leukocytes, and platelets, for leukocyte transmigration during hepatic ischemia-reperfusion (I/R) in vivo. We show that JAM-A is up-regulated in hepatic venular endot...

Leukocyte adhesion deficiency II (LAD II), also known as congenital disorder of glycosylation IIc (CDG-IIc), is a human disease in which a defective GDP-fucose transporter (SLC35C1) causes developmental defects and an immunodeficiency that is based on the lack of fucosylated selectin ligands. Since the study of in vivo leukocyte trafficking in patients with LAD II is experimentally limited, we ...