Leukocyte adhesion deficiency syndrome: insights into the molecular basis of leukocyte emigration.
Important insights into the molecular basis of leukocyte emigration have come from studies of the leukocyte adhesion deficiency (LAD) syndrome, a rare heritable disorder caused by deficiency of the leukocyte beta 2 integrin receptor CD11/CD18. Severely affected patients exhibit a profound defect in neutrophil emigration to tissue. In vitro and in vivo studies demonstrate that the CD11/CD18 complex is the major determinant of the firm adhesion and transendothelial migration of neutrophils. The inability of CD11/CD18-deficient neutrophils to adhere to and migrate across endothelium results in a profound defect in neutrophil emigration to tissue which leads to recurrent infection. The careful investigation of the LAD syndrome has also helped to characterize CD11/CD18-independent adhesion pathways such as the selectin receptors and the beta 1 integrin receptor VLA-4. Interestingly, although the LAD syndrome clearly establishes the importance of the beta 2 integrin receptors in host defense, inhibition of CD11/CD18 function may represent a novel approach to the therapy of inflammatory and immune disorders.
Division of Hematology, University of Washington, Seattle 98195.
J M
JM
Harlan
D002448:Cell Adhesion; D002465:Cell Movement; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000473:pathology*; D007962:Leukocytes / Q000166:cytology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology
D016201:Receptors, Lymphocyte Homing