The Leukocyte Integrins

This chapter focuses on the molecular biology of the leukocyte integrins, LFA-1, Mac-1, and p150,95, and on their role in mediating inflammation. Three recent developments have underscored the importance of the leukocyte integrins as adhesion receptors of the immune system: The recognition that the leukocyte integrins are evolutionarily related to other integrins; Identification of intercellular adhesion molecule-1 (ICAM-l), a ligand for LFA-1, which is induced during inflammation, and may regulate leukocyte migration and localization; and discovery and characterization of immunodeficiency patients who are genetically deficient in their expression of the leukocyte integrins. Researchers have found a class of immune-deficient patients who suffer from recurrent, life-threatening bacterial and fungal infections, and who have neutrophils deficient in chemotaxis and phagocytosis. Infected, necrotic lesions in these patients contain few leukocytes, despite the observation that these patients have chronic leukocytosis. The leukocyte integrins are α1β1 heterodimers, in which the α subunit is noncovalently associated with the β subunit. The α subunits of LFA-1, Mac-1, and p150, 95 are 1,80,000, 1,70,000, and 1,50,000 Da, respectively. The α subunits have been shown to be distinct by MAb reactivity, antigen-preclearing studies, and tryptic peptide mapping. In contrast, the β subunit, Mr = 95,000, has been shown to be identical in all three proteins by the same criteria. There is also substantial evidence that other ligands for LFA-1, Mac-1, and p150, 95 exist. Rational strategies must be designed to identify these ligands and to assess their contributions in different phases of the immune response. Multiple ligands may provide quite distinct signals and positional information to leukocytes.