Leukocyte adhesion deficiencies

  title={Leukocyte adhesion deficiencies},
  author={Suhair Hanna and Amos Etzioni},
  journal={Annals of the New York Academy of Sciences},
Leukocyte trafficking from the blood stream to tissues is essential for continuous surveillance of foreign antigens. This dynamic process, designated as the leukocyte adhesion cascade, involves distinct steps. In leukocyte adhesion deficiency (LAD) I the firm adhesion of leukocyte to the endothelium is defective, due to mutations in the beta 2 integrin gene. LAD II is caused by mutations in the fucose transporter specific to the Golgi apparatus, leading to the absence of Sialyl Lewis X—the… 

Leukocyte Adhesion Deficiency III - When Integrins Activation Fails

While several hundreds of patients with LAD I have been reported, LAD III was described in less than 20 patients, and it was proposed that this group, of all integrins activation disorder, be designated as LADIII.

Leukocyte adhesion deficiencies.

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections.

Selectin-Mediated Signaling—Shedding Light on the Regulation of Integrin Activity in Neutrophils

Molecular mechanisms involved in selectin-mediated signaling pathways in neutrophils and their impact on integrin activation, neutrophil recruitment, and inflammatory diseases are reviewed.

Characterization of kindlin3 in Integrin functions

A novel interaction between kindlin3 and receptor for activated-C kinase 1(RACK1) is identified, dependent on the pleckstrin homology (PH) domain ofkindlin3, which provides evidence that integrin β2 cytoplasmic tail, kindlin 3 and RACK1 can potentially form a ternary complex.

LFA1 Activation: Insights from a Single-Molecule Approach

This review summarizes integrin regulation and discusses new findings regarding the bidirectionality of LFA1 activation and signaling processes in lymphocytes.

A Novel Mutation in Leukocyte Adhesion Deficiency Type II/CDGIIc

Two Turkish siblings with a novel mutation in GFTP are described, both of which have the characteristic features of the syndrome.



Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options.

  • Amos Etzioni
  • Medicine, Biology
    Advances in experimental medicine and biology
  • 2007
It is clear that all hematopoietic integrin activation processes are defective, which lead to severe infection as observed in LAD I and to marked increase tendency for bleeding problems.

Genetic etiologies of leukocyte adhesion defects.

  • Amos Etzioni
  • Biology, Medicine
    Current opinion in immunology
  • 2009

Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation

It is shown that transfection of the subjects' lymphocytes with KINDLIN3 complementary DNA but not CALDAGGEF1 cDNA reverses the LAD-III defect, restoring integrin-mediated adhesion and migration.

Leukocyte adhesion deficiencies.

A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets

Two new LAD cases are reported in which lymphocytes, neutrophils, and platelets share severe defects in β1, β2, and β3 integrin activation, and CalDAG-GEFI is identified as a critical regulator of inside-out integrinactivation in human T lymphocytes.

Kindlin-3 is required for β2 integrin–mediated leukocyte adhesion to endothelial cells

Kindlin- 3 is essential to activate the β1, β2 and β3 integrin classes, and loss of Kindlin-3 function is sufficient to cause a LAD-III–like phenotype in mice.

Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter.

A novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient is reported, showing that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required.

Leukocyte adhesion deficiency II

This review focused on the current controversies, and open questions that have arisen from recent studies on the genetic defect, therapy and the basis of psychomotor defects in LAD II.

Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III.

It is shown that the product of a single gene, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), controlled the activation of all 3 integrins in the hematopoietic system.