Molecular Basis for Leukocyte Adhesion Molecule Deficiency
Adhesion of leukocytes to other cells and to the extracellular matrix has now been established as a critical component in acute and chronic inflammatory reactions (Moller, 1990). This process involves a number of adhesion molecules belonging to several gene families, including the selectins, integrins, and immunoglobulins. The biologic importance of this process has been established in part through an understanding of the pathogenesis of a rare disease, Leu-CAM deficiency. In this disease, leukocytes from affected individuals have lost either partially or completely their ability to adhere to and migrate across endothelium and subendothelial matrix at inflammatory sites and to phagocytose invading bacteria. Affected individuals consequently suffer from recurrent and often fatal bacterial infections despite the presence of neutrophilia. Biopsies of infected tissues often reveal numerous bacteria, lymphocytes, and plasma cells, with very few neutrophils. Blood vessels at the inflammatory sites, however, often are congested and dilated and contain numerous neutrophils. The defects in extravasation and ingestion were traced through a series of studies in the early 1980s to defective expression of three surface glycoprotein heterodimers, Leu-CAMs (CD 11/CD 18, β 2 integrins), now known to be members of the large integrin family (Hynes, 1987; Ruoslahti, 1991). The same disease was subsequently identified in dogs (Giger et al., 1987) and in cattle (Kehrli et al., 1990). In the latter case, the disease is also known as the granulocytopathy syndrome and is an important cause of mortality in young Holstein cattle.
KeywordsChronic Myelogenous Leukemia Leukocyte Adhesion Leukocyte Adhesion Deficiency Recurrent Bacterial Infection Cell BioI
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