title: Possible control of cell death pathways in ataxia telangiectasia. A case report.
abstract: Peripheral blood monocytes (PBMCs) obtained from a boy with the neuroimmunodegenerative syndrome of ataxia telangiectasia (AT) failed to aggregate or replicate efficiently when mitogenically activated under serum-depleted conditions. These cells rapidly swelled, then slowly shrank, and flattened as they excreted vesicles containing chromatin. This accelerated cell death with loss of homoadhesiveness could be prevented in vitro in most of the homozygous PBMCs by adding large amounts of autologous serum or by adding mixtures of Th1 cytokines, serum factors, and redox agents. However, even in high-serum media containing added cytokines, 20-30% of the homozygous PBMCs quickly flattened, produced minicells, and died. Since the defective functions of the human ataxia-telangiectasia nuclear kinase gene (ATM) could be bypassed in vitro in these defective AT PMBCs by addition of appropriate cytokines and redox survival factors, it may be possible to slow the progressive losses of ATM-deficient lymphoid cells seen in vivo. Since the neuronal degeneration in AT, as seen in the retrovirus-induced neuroimmunodegenerative syndromes, may also be a consequence of impairment of the central and peripheral immune system, it may become possible to prevent the neurodegeneration in AT by using signaling therapies that upregulate the ATM-induced signal deficiencies in the developing immune system.
authors.affiliation: Science Park--Research Division, M.D. Anderson Cancer Center, University of Texas, Smithville 78957, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Lynn
authors.forename: P K
authors.initials: PK
authors.lastname: Wong
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000473:pathology; D001260:Ataxia Telangiectasia / Q000097:blood / Q000276:immunology / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001685:Biological Factors / Q000097:blood / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D018797:Cell Cycle Proteins; D048429:Cell Size; D002478:Cells, Cultured; D002648:Child; D004268:DNA-Binding Proteins; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D016131:Lymphocyte Subsets / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D015213:Neuroimmunomodulation; D009474:Neurons / Q000473:pathology; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D000111:Acetylcysteine; D064007:Ataxia Telangiectasia Mutated Proteins; D001685:Biological Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; D008222:Lymphokines; D019869:Phosphatidylinositol 3-Kinases; D010835:Phytohemagglutinins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D013936:Thymidine; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human