Effects of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the expression of LFA-1 in the moderate phenotype of leukocyte adhesion deficiency (LAD).
Leukocyte adhesion deficiency (LAD) is a recessive autosomal disease characterized by life-threatening recurrent bacterial infections, associated with defective functions of leukocytes due to deficient membrane expression of leukocyte adhesion glycoproteins. These proteins, LFA-1, Mac-1 (CR3), and p150,95 are alpha 1 beta 1 heterodimers composed of different alpha chains noncovalently associated with a common beta chain. Patients with the severe phenotype of the disease completely lack the three glycoproteins on leukocyte surfaces, while patients with the moderate phenotype can express low levels of leukocyte adhesion proteins (1-10%). We have studied a patient with the moderate phenotype of LAD. Polymorphonuclear functions such as chemotaxis and adherence were altered, natural killer activity was low, and cytotoxic T-lymphocyte activity was abolished. Previous biochemical studies showed a conserved synthesis of both the LFA-1 alpha-chain precursor and the beta-chain precursor with, occasionally, some amount of alpha-beta complexes in the cytosol. beta chain-specific mRNA transcripts of normal size were detected at normal levels in patients' cells. Attempts to increase the transcription of the beta gene by in vitro treatment with TNF-alpha or IFN-gamma were successful but did not result in increased membrane expression of the alpha-beta complexes.
Dimanche-Boitrel
M T
MT
Immunologie et Rhumatologie Pédiatriques, INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Le Deist
F
F
Quillet
A
A
Fischer
A
A
Griscelli
C
C
Lisowska-Grospierre
B
B
D000943:Antigens, Differentiation / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000032:analysis; D015152:Blotting, Northern; D018821:CD18 Antigens; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D002633:Chemotaxis; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D010641:Phenotype; D012313:RNA / Q000032:analysis; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D007371:Interferon-gamma