Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets.
The role of LFA-1, a member of the integrin supergene family, in intercellular adhesion, including lymphocyte-endothelial cell (EC) binding, has been established. We now demonstrate that differences in LFA-1 cell surface density are responsible for the variable adhesion efficiency of lymphocyte subsets to EC. Electrophoretic analysis revealed multiple glycosylated isoforms of both alpha and beta subunits, largely as a result of different degrees of sialylation, with variable expression among different lymphocyte subsets. Neuraminidase digestion before EC adhesion increased the binding efficiency of all lymphocyte subsets, although the relative increase in each subset was proportional to the initial LFA-1 sialic acid content. LFA-1 cross-linking resulted in phosphoinositide hydrolysis and a rise in [Ca2+]i when using anti-alpha but not anti-beta subunit antibodies. These findings indicate that the density of LFA-1 on lymphocyte subsets controls their adhesive properties, and that the LFA-1 alpha subunit has transmembrane signaling properties that may result in activation events after interaction with its natural ligands.
Pardi
R
R
Department of Internal Medicine, CNR, Milano, Italy.
Bender
J R
JR
Dettori
C
C
Giannazza
E
E
Engleman
E G
EG
D000328:Adult; D000943:Antigens, Differentiation / Q000502:physiology*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D003432:Cross-Linking Reagents; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D007399:Interphase; D016169:Lymphocyte Function-Associated Antigen-1; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D019158:N-Acetylneuraminic Acid; D010716:Phosphatidylinositols / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D012794:Sialic Acids / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D010716:Phosphatidylinositols; D016028:Receptors, Leukocyte-Adhesion; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid